Manual of Clinical Nephrology [First Edition] 9789354665288

Table of contents :
Cover
Half Title Page
Title Page
Copyright
Foreword by Matiur Rahman
Foreword by Kanak Kanti Barua
Preface
Contents
1. Short Cases
2. Structured Clinical Assessment (SCA)
3. Instrument and Specimen
4. Radiology and Imaging
5. Transplant Work Up
Index
Back Cover

Citation preview

Manual of

Clinical

Nephrology

Manual of

Clinical

Nephrology Muhammad Rafiqul Alam

MBBS, MD, FCPS

Professor Department of Nephrology Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, Bangladesh

CBS Publishers & Distributors Pvt Ltd New Delhi • Bengaluru • Chennai • Kochi • Kolkata • Mumbai Bhopal • Bhubaneswar • Hyderabad • Jharkhand • Nagpur • Patna • Pune • Uttarakhand • Dhaka (Bangladesh) • Kathmandu (Nepal)

Disclaimer Science and technology are constantly changing fields. New research and experience broaden the scope of information and knowledge. The authors have tried their best in giving information available to them while preparing the material for this book. Although, all efforts have been made to ensure optimum accuracy of the material, yet it is quite possible some errors might have been left uncorrected. The publisher, the printer and the authors will not be held responsible for any inadvertent errors, omissions or inaccuracies. eISBN: xxxx Copyright © Authors and Publisher First eBook Edition: 2020 All rights reserved. No part of this eBook may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system without permission, in writing, from the authors and the publisher. Published by Satish Kumar Jain and produced by Varun Jain for CBS Publishers & Distributors Pvt. Ltd. Corporate Office: 204 FIE, Industrial Area, Patparganj, New Delhi-110092 Ph: +91-11-49344934; Fax: +91-11-49344935; Website: www.cbspd.com; www.eduport-global.com; E-mail: [email protected]; [email protected] Head Office: CBS PLAZA, 4819/XI Prahlad Street, 24 Ansari Road, Daryaganj, New Delhi-110002, India. Ph: +91-11-23289259, 23266861, 23266867; Fax: 011-23243014; Website: www.cbspd.com; E-mail: [email protected]; [email protected].

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Representatives Hyderabad Pune Nagpur Manipal Vijayawada Patna

Foreword

I

t is of immense pleasure for me to write the Foreword to Manual of Clinical Nephrology written by Dr Muhammad Rafiqul Alam. I believe that this book will be of great help for the examinees of different postgraduate courses of nephrology. Some short cases, structured clinical assessment (SCA) stations and instruments are discussed in this book. FCPS and MD (nephrology) students will get some idea about how to prepare themselves for final examinations. I wish this book all success.

Matiur Rahman Founder of nephrology discipline in Bangladesh

Foreword

I

am pleased to observe that Manual of Clinical Nephrology written by Dr Muhammad Rafiqul Alam will be of great help for the MD residents and nephrology fellowship examinees. This book has been compiled exactly in the way how we expect our students should learn clinical nephrology. I believe this book will enrich the knowledge and skill armamentarium of the fellows in renal medicine. I wish this book all success.

Kanak Kanti Barua Vice-Chancellor Bangabandhu Sheikh Mujib Medical University Dhaka, Bangladesh

Preface

F

or a long time I am being involved in fellowship examination in nephrology and Phase B final examination of MD residents in nephrology. From my experience in conducting fellowship and MD (Residency) examinations, I have tried to discuss some short cases, structured clinical assessment (SCA) stations, instruments, and images, etc., in this book, so that the examinees get some idea about how to prepare themselves for the examinations. The book has been laid down in five chapters, viz. short cases, structured clinical assessment (SCA), instruments and specimen, radiology and imaging and transplant work up. I would like to express my heartfelt thanks and gratefulness to my students specially Dr Obaid, Dr Faisal, Dr Tahmid and others who helped me a lot in compiling the book and thanks to my wife, daughters, son-in-laws, granddaughter and grandson for their emotional and social supports. I am also thankful to my colleagues for constructive criticism and valuable support. Special thanks to Mr KM Haque for the wonderful service in preparing the manuscript. The deficits that would have been noted in the current edition will be hopefully corrected in the future edition. Finally, all praises go to the Almighty.

Muhammad Rafiqul Alam

Contents Foreword by Matiur Rahman Foreword by Kanak Kanti Barua Preface

1. Short Cases

v vii ix

1

2. Structured Clinical Assessment (SCA)

37

3. Instrument and Specimen

65

4. Radiology and Imaging

79

5. Transplant Work Up

92

Index

101

1

Short Cases Scenario

Q1. Look at the face and tell your findings. Ans. The face is puffy and plethoric (moon face). There is also acne and hirsutism. Q2. What is the likely diagnosis? Ans. Cushing’s syndrome. Q3. What else do you want to see or examine? Ans. I want to examine neck (to see buffalo hump, supraclavicular fat deposition), striae (in different parts of the skin), proximal myopathy, bone pain due to osteoporosis, blood pressure and urine sugar. Q4. What are the causes of moon face or puffy face? Ans. • Simple obesity. 1

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Manual of Clinical Nephrology

• Cushing’s syndrome (plethoric face, with hirsutism, acne). • Myxedema (puffy face with baggy eyelids, fall of lateral eyebrows, malar flush). • Nephrotic syndrome and acute glomerulonephritis (puffy face with periorbital oedema). • Superior vena caval obstruction (engorged and non-pulsatile veins, plethoric face with subconjunctival suffusion). • Angioedema (localized, swollen lip or face). • Chronic alcoholism (plethoric, puffy face). • Surgical emphysema (history of trauma, also swelling is extended up to the neck and chest and there is multiple crepitus on palpation). Q5. Name some diseases where steroid is used for prolonged period. Ans. Addison’s disease, SLE, glomerulonephritis, pemphigus vulgaris, dermatomyositis, severe rheumatoid arthritis, hypopituitarism, diffuse parenchymal lung disease (DPLD), etc. Q6. Mention one absolute indication of steroid therapy. Ans. Addison’s disease (also pemphigus vulgaris) Q7. Why backache in Cushing’s syndrome? Ans. Osteoporosis (may cause vertebral collapse and kyphosis). Q8. What is the character of striae in Cushing’s syndrome? Ans. Striae are pink or purple colored in the skin of abdomen and other parts of body. Q9. What are the eye complications in Cushing’s syndrome? Ans. Cataract. Q10. What is Cushing’s syndrome? What are the common features? Ans. It is defined as constellation of symptoms and signs characterized by prolonged glucocorticoid excess due to any cause. Common features are: • Weight gain but weakness, lethargy. • Proximal muscular weakness (characterized by difficulty in combing, raising hands above head, standing from squatting). • Backache, pathological fracture (due to osteoporosis), collapse of the vertebra with reduction of height. • Easy bruising, purple striae. • In female: Amenorrhea or oligomenorrhoea, hirsutism. • Loss of libido. • Frequent infection, especially fungal infection, slow wound healing. • Hypertension, DM (30%) or IGT. • Mood disturbance such as depression, insomnia, irritability. • On examination: Moon face, buffalo hump, truncal obesity, hirsutism, acne on face, pink striae, growth retardation in children.

Short Cases

3

Q11. What is the difference between Cushing’s disease and Cushing’s syndrome? Ans. • Cushing’s disease is caused by increased ACTH secretion from pituitary gland that stimulates adrenals, causing excess cortisol secretion. • Cushing’s syndrome is caused by excess steroid (cortisol) due to any cause. Q12. How to investigate Cushing’s syndrome? Ans. First to confirm the diagnosis and then further tests to find out the cause. Tests to confirm Cushing’s syndrome. Screening test: • 24 hours’ urinary free cortisol measurement. • Or, overnight dexamethasone suppression test (see below). • Or, low dose dexamethasone suppression test (see below). • Or, late night salivary cortisol. • Or, circadian rhythm i. If normal, Cushing’s syndrome is unlikely. ii. If anyone is abnormal, perform other tests and repeat the abnormal result. • Cushing’s syndrome is confirmed by using 2 of 3 main tests: i. Failure to suppress serum cortisol with low doses of oral dexamethasone. ii. Loss of normal circadian rhythm of cortisol, with inappropriately elevated late night serum or salivary cortisol. iii. Increased 24-hour urine free cortisol. If Cushing’s syndrome is confirmed, other tests are done to find out the cause (to localize the site of lesion): Serum ACTH • If ACTH is low or undetectable: Adrenal cause is likely. Then USG, CT or MRI to find adrenal lesion (tumor or hyperplasia). If no mass is seen, then adrenal vein sampling or adrenal scintigraphy should be done. • If ACTH is high: Likely cause in pituitary (Cushing’s disease) or ectopic ACTH syndrome. Other tests (to see the effect) • Electrolytes (hypokalemia). • Blood sugar. • Bone mineral densitometry to see osteoporosis.

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Manual of Clinical Nephrology

Scenario Instruction: Examine the abdomen and relevant.

Inspection • There is an oblique scar mark in the right iliac fossa • Left brachiocephalic arteriovenous fistula with development of aneurysm • Bruising over the A-V fistula Palpation There is a bean-shaped mass in right iliac fossa, surface is smooth, margin is ill defined, no tenderness, no organomegaly, kidneys are not ballotable, no ascites, bowel sound present and no added sound. Q1. What are the relevants you want to see? To assess graft function • Anaemia • Edema (other feature of fluid overload) • A-V fistula: Whether it is active (prick mark) and functioning (thrill and bruit)

Side Effects of Drug (from Head to Toe) • Acne, gum hypertrophy, tremor, hirsutism • Abdomen: Striae, thinning of skin • Fungal infection, viral warts, skin malignancy Blood Pressure: On Medication/Not Etiology of CKD • DM → prick mark in fingers (blood glucose testing), insulin injection mark • ADPKD → If removed before transplantation, scar mark may be present • Double scar mark → Previous native kidney nephrectomy as per indication

Short Cases

5

Any Sign of/Previous Mode of RRT • JVC, FVC or PD catheter scar mark Previous failed allograft: Mass in iliac fossa both right and left Bed side urine examination Q2. What is your diagnosis? Transplant kidney Q3. What are the immunosuppressive drugs used in renal transplantation? • For induction, biologic agents are used as part of the initial immunosuppressive regimen in kidney transplant recipient (KTR) • For maintenance immunosuppression, CNI (tacrolimus be the first-line CNI), an anti-proliferative agent (mycophenolate mofetil be the first-line agent) and with or without corticosteroid Q4. What are the common side effects of immunosuppressive drugs? • CNI: – Nephrotoxicity – Hypertension and sodium retention → more with cyclosporine – Cosmetic:  Cyclosporine → gum hypertrophy, hypertrichosis  Tacrolimus → Alopecia – Metabolic:  Tacrolimus → NODAT  Cyclosporine → hyperuricemia, dyslipidemia: hypomagnesemia, hyperkalemia: CsA and Tac – GI intolerance: Tacrolimus – Neurotoxicity: Tremor, headache, insomnia → Tacrolimus • MMF: – GI side effects → nausea, vomiting, diarrhea – Bone marrow suppression → leukopenia, anemia, thrombocytopenia • Azathioprine: – Hematologic side effect → leukopenia, anemia, thrombocytopenia – Pancreatitis → rarely, also hepatitis and cholestasis • mTOR inhibitors: – Nephrotoxicity → de novo proteinuria, nephritic syndrome and exacerbation of pre-existing proteinuria  Impaired wound exacerbation healing  Hyperglycemia, hyperlipidemia  Pneumonia  Bone marrow suppression • Corticosteroid: Cosmetic changes, growth impairment, osteoporosis, osteonecrosis impaired wound healing, cataract, glucose intolerance and psychologic effects

Manual of Clinical Nephrology

6

Q5. How will you monitor drug level? • For cyclosporine: C2 level (2-hour post dose)/C0 (12-hour trough) • For tacrolimus: C0 level (12-hour trough) • For MMF: MPA AUC Q6. Suppose, this patient is a renal allograft recipient for last 2 years, presented to you with several episodes of loose stool for last 3 months which is mucoid and not blood mixed. He is on tacrolimus, MMF and prednisolone. What are the differentials you will consider?

Differential Diagnosis Most common: • Immunosuppressive drugs particularly MMF induced • CMV colitis • Post-transplant lymphoproliferative disease (PTLD) Other differentials: • Bacterial infection: C. difficle, C. jejuni, E. coli • Viral infection: Norovirus, adenovirus • Fungal and parasitic: Microsporidia, cryptosporidia, isospora belli, amoebiasis and giardiasis, Strongyloides stercoralis • Also, non-immunosuppressive medication should be considered.

Brief Discussion about Fluid Protocol in Post-transplant Period Urine output

Type and sequence of IV fluid infusion

100 ml/hr

Add 50 ml to output

DA/NS/DA/NS

100–300 ml/hr

Add 25 ml to output

DA/NS/DA/NS/HS

300–500 ml/hr

Give exact amount of output

DA/NS/HS

> 500 ml/hr

Give 50 ml less to the output

DA/HS/NS/HS

*5% dextrose in aqua (DA) then 0.9% normal saline (NS) then 5% dextrose in aqua (DA) then 0.9% normal saline (NS). HS: Hartmann’s solution

Warm Ischemia Time and Cold Ischemia Time There are 3 potential periods for ischemic injury during kidney transplant. • First, ischemia during organ retrieval, from the time of cross clamping (or of asystole in non-heart-beating donors), until cold perfusion is commenced. • Second, there is a period of cold ischemia time (CIT), defined as the period wherein the kidney is transported from donor to recipient on ice or pump perfused under hypothermic conditions. This is followed lastly by a period of warm ischemia time (WIT) during reanastomosis in the recipient (“recipient WIT”) between the period that the kidney is taken out of cooling and the time that it is reperfused by the recipient’s blood. A prolonged recipient WIT has been associated with poor short- and long-term graft outcomes.

Short Cases

7

Delayed Graft Function Delayed graft function (DGF) has been defined as the need for dialysis within the first week after transplantation. Differential diagnosis of renal allograft dysfunction • Ureteric obstruction • Renal artery stenosis • Glomerulonephritis: Recurrent and de novo • Infection: – polyomavirus nephropathy – recurrent pyelonephritis/vesicoureteric reflux • Nephrotoxic agents • Late/recurrent acute rejection – non-compliance – iatrogenic • Chronic allograft nephropathy – sclerosing non-specific tubulo-interstitial damage – chronic cellular rejection – chronic humoral rejection – calcineurin inhibitor nephrotoxicity – transplant glomerulopathy

POST-TRANSPLANT Administering antimicrobial therapy to all at-risk patients immediately after transplantation for a defined duration dependent on the perceived duration of risk and net state of immunosuppression.

Post-transplant Antimicrobial Prophylaxis Prophylaxis

Regimen

Comments

Pneumocystis jirovecii

First line: TMP-SMX × 6 months Second line (sulphur allergies): Atovaquone, dapsone or aerosolized pentamidine

TMP-SMX also reduces the incidence of Toxoplasma gondii, Listeria monocytogenes, and Nocardia asteroids and reduces the incidence of UTI in kidney transplant recipients.

Fungal

Nystatin S & S (× 1 month) or fluconazole (× 3–6 months)

Fluconazole recommended in high-risk recipients (e.g. combined liver–kidney or pancreas–kidney transplant recipients, history of coccidioidomycosis, patients who live in endemic areas)

CMV

Acyclovir, ganciclovir, or valganciclovir Acyclovir for HSP and VZV prophylaxis for patients not on CMV prophylaxis

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Manual of Clinical Nephrology

Main factors contributing to late graft injury and late graft loss • Donor factors – Deceased donor kidney (DBO or DCD) – Female gender – Vascular disease – Comorbidity – Prolonged ischemia time – Delayed graft function • Recipient risks (nonimmune) – Obesity – Urinary tract infection – Transplant ureteral obstruction – Graft pyelonephritis – Polyoma (BK) virus nephropathy – Calcineurin inhibitor nephrotoxicity – Recurrent pyelonephritis – Hypertension, dyslipidemia, smoking – Diabetes (pre-existing or post-transplantation) • Recipients risks (alloimmune) – Child or adolescent recipient – Variable medication through concentration from malabsorption or nonadherence – HLA mismatches, presensitization status (donor-specific HLA alloantibodies) – Acute rejection that is severe, corticosteroid resistant, vascular, antibody-mediated or late occurring – Late de novo donor-specific antibodies and chronic (antibody-mediated) rejection.

KDIGO GUIDELINE RECOMMENDATIONS INDUCTION THERAPY Starting a combination of immunosuppressive medications before, or at the time of, kidney transplantation. Including induction therapy with a biologic agent as part of the initial immunosuppressive regimen in kidney transplant recipients (KTR). • An IL2-RA be the first-line induction therapy. • Using a lymphocyte-depleting agent, rather than an IL2-RA, for KTRs at high immunologic risk. Initial Maintenance Immunosuppressive Medications Using a combination of immunosuppressive medications as maintenance therapy including a CNI and an anti-proliferative agent, with or without corticosteroids. Tacrolimus be the first-line CNI used. • Tacrolimus or CsA be started before or at the time of transplantation, rather than delayed until the onset of graft function.

Short Cases

9

Mycophenolate be the first-line anti-proliferative agent. Patients who are at low immunological risk and who receive induction therapy, corticosteroids could be discontinued during the first week after transplantation. If mTORi are used, they should not be started until graft function is established and surgical wounds are healed.

Long-term Maintenance Immunosuppressive Medications • Using the lowest planned doses of maintenance immunosuppressive medications by 2–4 months after transplantation, if there has been no acute rejection. • CNIs be continued rather than withdrawn. • If prednisone is being used beyond the first week after transplantation, prednisone be continued rather than withdrawn. STRATEGIES TO REDUCE DRUG COSTS If drug costs block access to transplantation, a strategy to minimize drug costs is appropriate, even if use of inferior drugs is necessary to obtain the improved survival and quality of life and other benefits of transplantation compared with dialysis. Strategies that may reduce drug costs include: • Limiting use of a biologic agent for induction to patients who are high-risk for acute rejection • Using ketoconazole to minimize CNI dose • Using a non-dihydropyridine CCB to minimize CNI dose • Using azathioprine rather than mycophenolate • Using adequately tested bioequivalent generic • Using prednisone long-term.

MONITORING IMMUNOSUPPRESSIVE MEDICATIONS Measuring CNI in blood • Every other day during the immediate postoperative period until target levels are reached • Whenever there is a change in medication or patient status that may affect blood levels • Whenever there is a decline in kidney function that may indicate nephrotoxicity or rejection. Monitoring • CsA using 12-h trough (C0), 2-h post-dose (C2), or abbreviated AUC. • Tacrolimus using 12-h trough (C0). • MMF levels. • mTORi levels.

TREATMENT OF ACUTE REJECTION (RECOMMENDATIONS) Biopsy should be done before treating acute rejection, unless the biopsy will substantially delay treatment.

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Manual of Clinical Nephrology

Subclinical and borderline acute rejection should be treated. Corticosteroids should be used for the initial treatment of acute cellular rejection. • Adding or restoring maintenance prednisone in patients not on steroids who have a rejection episode. • Using lymphocyte-depleting antibodies or OKT3 for acute cellular rejections that do not respond to corticosteroids, and for recurrent acute cellular rejection. Treating antibody-mediated acute rejection with one or more of the following alternatives, with or without corticosteroids • Plasma exchange; • Intravenous immunoglobulin; • Anti-CD20 antibody; • Lymphocyte-depleting antibody. For patients who have a rejection episode, adding mycophenolate if the patient is not receiving mycophenolate or azathioprine, or switching azathioprine to mycophenolate.

TREATMENT OF CHRONIC ALLOGRAFT INJURY (CAI) Kidney allograft biopsy should be done for all patients with declining kidney function of unclear cause, to detect potentially reversible causes. For patients with CAI and histological evidence of CNI toxicity, reducing, withdrawing, or replacing the CNI is recommended. • For patients with CAI, eGFR >40 ml/min/1.73 m2, and urine total protein excretion of 500 mg per gram creatinine (or equivalent proteinuria by other measures), replacing the CNI with a mTORi may be done.

MONITORING KIDNEY ALLOGRAFT FUNCTION Measuring urine volume • Every 1–2 hr for at least 24 hr after transplantation; • Daily until graft function is stable. Measuring urine protein excretion, at least • Once in the first month to determine a baseline • Every 3 months during the first year • Annually, thereafter. Measuring serum creatinine, at least • Daily for 7 days or until hospital discharge, whichever occurs sooner • 2–3 times per week for weeks 2–4 • Weekly for months 2 and 3 • Every 2 weeks for months 4–6 • Monthly for months 7–12 • Every 2–3 months, thereafter. Estimating GFR whenever serum creatinine is measured.

Short Cases

11

Including a kidney allograft ultrasound examination as part of the assessment of kidney allograft dysfunction.

KIDNEY ALLOGRAFT BIOPSY • • • •

When there is a persistent, unexplained increase in serum creatinine. When serum creatinine has not returned to baseline after treatment of acute rejection. Every 7–10 days during delayed function. If expected kidney function is not achieved within the first 1–2 months after transplantation. • When there is – new onset of proteinuria; – unexplained proteinuria >3.0 g per gram creatinine or >3.0 g/24 hr.

VIRAL DISEASES BK (Polyoma) Virus Screening all KTRs for BKV with quantitative plasma NAT at least: • Monthly for the first 3–6 months after transplantation • Then every 3 months until the end of the first post-transplant year • Whenever there is an unexplained rise in serum creatinine • After treatment for acute rejection. Immunosuppressive medications should be reduced when BKV plasma NAT is persistently greater than 10,000 copies/ml (107 copies/L). Cytomegalovirus CMV prophylaxis: KTRs (except when donor and recipient both have negative CMV serologies) should receive chemoprophylaxis for CMV infection with oral ganciclovir or valganciclovir for at least 3 months after transplantation, and for 6 weeks after treatment with a T-cell-depleting antibody. In patients with CMV disease, weekly monitoring of CMV by NAT or pp65 antigenemia should be done. CMV Treatment • All patients with serious (including most patients with tissue invasive) CMV disease be treated with intravenous ganciclovir. • CMV disease in adult KTRs that is not serious (e.g. episodes that are associated with mild clinical symptoms) be treated with either intravenous ganciclovir or oral valganciclovir. • All CMV diseases in pediatric KTRs be treated with intravenous ganciclovir. • Continuing therapy until CMV is no longer detectable by plasma NAT or pp65 antigenemia. Reducing immunosuppressive medication in life-threatening CMV disease, and CMV disease that persists in the face of treatment, until CMV disease has resolved. • Monitoring of graft function closely during CMV disease.

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Manual of Clinical Nephrology

URINARY TRACT INFECTION • All KTRs receive UTI prophylaxis with daily trimethoprim-sulfamethoxazole for at least 6 months after transplantation. • For allograft pyelonephritis, initial hospitalization and treatment with intravenous antibiotics should be done.

PNEUMOCYSTIS Jirovecii pneumonia • All KTRs receive PCP prophylaxis with daily trimethoprim sulfamethoxazole for 3–6 months after transplantation. • All KTRs receive PCP prophylaxis with daily trimethoprim-sulfamethoxazole for at least 6 weeks during and after treatment for acute rejection. • KTRs with PCP diagnosed by bronchial alveolar lavage and/or lung biopsy be treated with high-dose intravenous trimethoprim-sulfamethoxazole, corticosteroids, and a reduction in immunosuppressive medication. • Treatment with corticosteroids for KTRs with moderate to severe PCP.

DIABETES MELLITUS Screening for New Onset Diabetes after Transplantation (NODAT) Screening all nondiabetic KTRs with fasting plasma glucose, oral glucose tolerance testing, and/or HbA1c at least: • Weekly for 4 weeks; • Every 3 months for 1 year and • Annually, thereafter. Screening for NODAT with fasting glucose, oral glucose tolerance testing, and/or HbA1c after starting, or substantially increasing the dose no, of CNIs, mTORi, or corticosteroids. Managing NODAT or Diabetes Present at Transplantation • If NODAT develops, consider modifying the immunosuppressive drug regimen to reverse or ameliorate diabetes, after weighing the risk of rejection and other potential adverse effects. • Consider targeting HbA1c 7.0–7.5%, and avoid targeting HbA1c p6.0%, especially if hypoglycemic reactions are common. • In patients with diabetes, aspirin (65–100 mg/d) use for the primary prevention of CVD be based on patient preferences and values, balancing the risk for ischemic events to that of bleeding. HYPERTENSION • Measuring blood pressure at each clinic visit. • Maintaining blood pressure at of 1 g/d for >18 years old, consider an ACE-I or an ARB as the first-line therapy.

Short Cases

13

Scenario

CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD) Q1. Examine the abdomen and tell your findings. Ans. Inspection: • There is tenckhoff peritoneal catheter • Catheter exit site is healthy • Abdomen is not distended, flanks are not full, umbilicus inverted Palpation: • There is no tenderness • There is no organomegaly Percussion: Shifting dullness is not positive Auscultation: Bowel sound is present. Q2. What are the frequency and duration of dialysis given by this catheter? Ans. • Patient performs manual exchange 3 to 5 times in a day. • Each exchange taking 30 minutes. Q3. What is the osmotic agent commonly used in CAPD? Ans. • Dextrose (glucose) • 1.5%, 2.5%, 4.25% dextrose preparations are commonly used • pH 5.5 Q4. What is the composition of dialysis solution used in CAPD? Ans. • pH 5.5 • Osmotic agent—glucose • Na: 132 mM, Ca: 1.75 mM, Mg: 0.75 mM, Lactate: 35 mM, Bicarbonate: 0 mM

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Manual of Clinical Nephrology

Q5. What are the non-glucose based solutions? Ans. Icodextrin, amino acid-based solution. Q6. Which patients are preferable for CAPD? Ans. 1. Patient with severe cardiovascular disease 2. Patient with difficult vascular access 3. Patient who desire greater freedom to travel and become active 4. Patient who wish to perform home dialysis 5. Infant and very young children Q7. What are the contraindications of CAPD? Ans. Unsuitable peritoneum due to the presence of adhesions, fibrosis and malignancy. Q8. What are the advantages of CAPD? Ans. 1. Less expensive than hemodialysis 2. Can be performed at home 3. Allow patient more independence and freedom to travel 4. Patient can take full responsibility for their treatment 5. Relatively low cost Q9. What are the disadvantages of CAPD? Ans. Less efficient than hemodialysis Q10. What are the complications of CAPD? Ans. 1. Peritonitis: Usually entry of skin contaminants via catheter, bowel organism is less common 2. Catheter exit site infection: Usually skin organism 3. Ultrafiltration failure: Damage of peritoneal membrane, leading to rapid transport of glucose and loss of osmotic gradient 4. Peritoneal membrane failure: Scarring or damage to peritoneal membrane 5. Sclerosing peritonitis Q11. What is the source of peritonitis? Ans. Intraluminal, periluminal, bowel source, hematogenous and transvaginal Q12. What are the common organism of peritonitis? Ans. • Gram-positive organism – S. aureus, coagulase negative staphylococcal species • Gram-negative organism – Pseudomonas sp. – E. coli • Fungi • Mycobacterium • Polymicrobial growth • Culture negative

Short Cases

15

Q13. What is the diagnostic criteria of peritonitis? Ans. At least 2 of the following 3 findings should be present: 1. Symptom and sign of peritoneal inflammation Symptoms: Abdominal pain, nausea and vomiting, feverish sensation, chills, constipation or diarrhea Signs: Cloudy peritoneal fluid, abdominal tenderness, rebound tenderness, increase temperature, blood leukocytosis 2. Cloudy peritoneal fluid with an elevated peritoneal fluid cell count (more than 100/mcL) due to predominantly neutrophil (more than 50%) and 3. Demonstration of bacteria in peritoneal effluent by Gram stain or culture Q14. What is the choice of antibiotics in peritonitis? Ans. Empiric antibiotics must cover both gram-positive and gram-negative organisms. Vancomycin or first generation cephalosporin such as cefazolin or cephalothin used in combination with an antibiotic such as ceftazidime or an aminoglycoside. Q15. What is sclerosing peritonitis? Ans. Sclerosing peritonitis is a rare form of peritoneal inflammation which involves parietal and visceral peritoneum characterized by fibrous thickening of peritoneum.

Scenario

Examination of the lower limbs

Inspection • Ulcer (site, single, multiple, oozing, gangrene, surrounding skin). • Look at the tip of all toes, sole and spaces between the toes.

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Manual of Clinical Nephrology

• If gangrene is present, see whether it is dry or wet, demarcation between healthy and unhealthy skin. • Color change of skin and hair loss. • Amputation of toe (may be). • Pigmented scar, small round plaques with raised border in a linear fashion over shin (diabetic dermopathy). • Joints (Charcot joint or joint swelling). • Thigh wasting, atrophy or hypertrophy (insulin therapy). Palpation: Ask the patient whether the foot is sore. • Temperature (warm or cold, compare with other foot). • Pulse (arteria dorsalis pedis, posterior tibial), reduced, absent or bounding. • Sensation, reduced or absent (see light touch, pain, joint sense). • Vibration and position sense (may be lost due to the posterior column lesion called diabetic pseudotabes). • Reflex, reduced or absent, see also plantar response. • In some cases, test for proximal myopathy (diabetic amyotrophy, which shows asymmetrical wasting of thigh). Q1. What is your diagnosis? Ans. Foot ulcer Q2. What are the causes of ulcer in DM? Ans. • Ischemia. • Neuropathy. • Combined ischemia and neuropathy. • Secondary infection. • Trauma. Q3. What is the pathology of ischemic ulcer? Ans. Usually macro vascular, associated with atherosclerosis. Q4. What are the findings, if the ulcer is due to combined neuropathy and ischemia? Ans. In such case, the findings are: • Ulcer is on foot, callosities and pressure points. • Loss of arch of foot. • Sensory loss of all modalities in stocking pattern. • Loss of pulsation. • Foot is cold, shiny with loss of hair.

Short Cases

17

Q5. What are the differences between ischemic and neuropathic ulcers or what are the features of neuropathic and ischemic ulcers? Ans. Causes of neuropathic ulcer: • Diabetes mellitus. • Leprosy. • Polyneuropathy (due to any cause). • Tabes dorsalis. • Syringomyelia. • Amyloidosis. • Porphyria. • Progressive sensory neuropathy. Features

Neuropathic ulcer

Ischemic ulcer (arterial)

Symptoms

No pain, paraesthesia or tingling may be present

Pain, history of claudication

Foot

High arched, clawing of toes, no trophic change

Rubor, trophic changes (atrophy and loss of hair)

Area

Warm, dry and pink

Cold, shiny

Pulse

Bounding

Absent or reduced

Sensation

Reduced or absent

Normal

Ulcer

Painless and mostly plantar

Painful, over heels and toes

Reflex

Reduced or absent, equivocal plantar response

Normal

Q6. What is diabetic foot? Ans. Diabetic foot is a group of disorders that occur as complication of diabetes mellitus. Presence of multiple pathology such as infection, diabetic foot ulcer and neuropathic osteoarthropathy is called diabetic foot syndrome. Q7. What are the features of diabetic foot? How to manage diabetic foot? Ans. 1. Neuropathic: Ulcer (plantar), sepsis, abscess, osteomyelitis, digital gangrene, Charcot joint, high arched and clawing of toes. 2. Ischemic: Ulcer, sepsis, gangrene. Management: Prevention is the main step. Along with good control of diabetes, following measures should be taken: 1. Advice to all diabetic patients: • Inspect and wash feet every day. • Miniaturization of skin, if dry. • Cut toe nails regularly, very carefully. • Wear suitable good-fitting shoes. • Check footwear for foreign bodies. • Change socks or stockings every day.

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Manual of Clinical Nephrology

• Avoid walking barefoot. • Cover minor cuts with sterile dressings. • Do not burst blisters. • Avoid over-the-counter corn or callus remedies. • Keep feet away from heat (e.g. hot water, hot sand, fire, radiation). 2. Additional advice to high-risk patients: • Do not attempt corn removal. • Avoid high and low temperature. 3. Involve a podiatrist in the care of the patient. 4. Special footwear should be used in Charcot neuroarthropathy. Q8. How to investigate diabetic ulcer? Ans. • CBC. • Blood sugar. • Urine RME. • X-ray of the affected part. • Doppler USG of the lower limb vessels. • C/S from pus, if any. • If localized area of occlusion—either bypass surgery or angioplasty may be needed. Q9. How to treat a case of diabetic ulcer? Ans. • Good control of diabetes mellitus. • Smoking should be stopped. • Local dressing and removal of dead tissue. • Antibiotic to control secondary infection. • Consult with chiropodist. • Surgery may be required (removal of callus, amputation or angioplasty). • Patient’s education: Avoid barefoot, tight shoes, careful cutting of nails, avoid weight bearing. • Other measures: As in diabetic foot. • Liaison should be maintained among physician, chiropodist and surgeon.

Short Cases

Scenario Instructions Examination of the lower limbs (perform general examination)

Presentation of the Case • The leg is swollen up to the thigh, red, warm with pitting edema • Tenderness in the calf muscle • Superficial veins are prominent and tender. Q1. What is the most possible diagnosis? Ans. Deep vein thrombosis Q2. What are the other possibilities? Ans. • Cellulitis • Ruptured Baker cyst • Post-traumatic calf hematoma Q3. What are the causes of DVT? Ans. • Prolonged bed rest or immobilization • Pregnancy and puerperium • Hypercoagulable state • Vascular damage Q4. What are the relevant investigations? Ans. • CBC, ESR • Serum albumin • Doppler USG of lower limb, D-dimer, venography • ANA, anti-ds-DNA, antiphospholipid antibody • Antithrombin III, protein C, protein S • Homocysteine level

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Q5. What are the complications of DVT? Ans. • Pulmonary embolism • Venous gangrene • Postphlebitic syndrome Q6. How to treat DVT? Ans. General management • Bed rest • Use of elastic stockings • Relief of pain by analgesics • Intermittent elevation of foot during day • Mobilization slowly when the patient is fully anticoagulated Anticoagulation • Unfractionated heparin • Low molecular weight heparin • Oral anticoagulant—warfarin IVC filters if anticoagulation contraindicated Q7. How to prevent DVT? Ans. • Early mobilization • Leg exercise • Elastic stockings • Low dose aspirin • Low molecular weight heparin • Avoid oral contraceptive pill • Treat the primary cause

Short Cases

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Scenario Instruction: Examine the arm

• Inspection: – Site of A-V access – Remaining part of the arm, shoulder, breast, neck and face – Presence of swelling (indicating suspicion of downstream swelling) – Presence of collateral veins (indicating suspicion of downstream swelling) – Any scar in the chest wall—evidence of previous catheterization – The presence of face, neck or breast swelling indicating central venous stenosis – Presence of aneurysm – Swelling and redness • Palpation: – Pulse:  Normally soft pulse  Water hammer pulse/hyperpulsatile pulse—in downstream stenosis  Feeble pulse in upstream stenosis – Thrill:  Felt as a ‘buzz’  It may be continuous/discontinuous (normally present if stenosis or obstruction) – Auscultation: (To see the quality of the bruit at the site of anastomosis)  Normally—continuous  If stenosis present—discontinuous bruit

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• Special test: – Pulse augmentation test to evaluate inflow segment  This is performed by complete occlusion of the access several centimeters beyond the arterial anastomosis  Test is considered to be normal if portion of the fistula upstream from the occluding finger demonstrates an augmentation of pulse  Normally:  The thrill should disappear.  The rest of the access upstream to the occluding finger should become hyperpulsatile. If thrill does not disappear, it indicates that there is a side branch of fistula draining (accessory outflow pathway should be suspected). – Arm elevation test to assess the outflow tract:  By elevating the extremity and examining the normal collapse of AV fistula  The test is considered abnormal when the fistula remains plump after arm elevation and fails to collapse  This indicates downstream obstruction

Possible Locations for Upper Arm AV Fistula A. Conventional 1. Snuffbox (distal-most site) 2. Radiocephalic or Brescia-Cimino (radial artery to forearm cephalic vein at the wrist) 3. Ulnar artery to forearm basilic vein (uncommon) 4. Brachial artery to upper arm cephalic vein (at the elbow) B. Transposed 1. Forearm basilic vein to radial artery at the wrist. 2. Forearm basilic vein to the brachial artery (loop configuration) 3. Forearm cephalic vein to the brachial artery (loop configuration) Complications of AV Fistula/AV Graft Immediate 1. Failure to primary maturation 2. Hemorrhage 3. Infection Delayed 1. Stenosis 2. Thrombosis 3. Inadequate blood flow 4. Ischemia 5. Edema

Short Cases

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6. Aneurysm 7. Pseudo aneurysm 8. Steal syndrome 9. Infections 10. Extravasation injury 11. SVC or central vein obstruction 12. Burst of fistula

Thrombosis of AV Fistula and Graft It is the most common complication of AV access and 80–85% of causes of access failure. Causes of Thrombosis 1. Stenosis 2. Vascular endothelial injury 3. Altered blood coagulability 4. Arterial stenosis 5. Fistula compression 6. Hypovolemia 7. Hypertension 8. Hematoma formation from cannulation injury 9. Hypercoagulable state Predisposing Factors 1. High fibrinogen state 2. Reduce level of protein S and protein C 3. Factor V Leiden mutation 4. Lupus anticoagulant 5. Increased hematocrit due to treatment with erythropoietin. Prevention 1. Regular monitoring of fistula and graft 2. Avoid hypotension and hypovolemia 3. Avoid early use of graft before maturation 4. Avoid venipuncture and BP measurement in fistula hand. 5. Prophylactic use of aspirin and warfarin (INR 1.6–1.9) Treatment 1. Treatment of AV fistula • Surgical and percutaneous intervention 2. Treatment of AV graft: • Endoluminal

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Manual of Clinical Nephrology

– Pharmacological thrombectomy – Percutaneous thrombectomy • Surgical thrombectomy – Depending upon expertise of the center 3. If there is residual stenosis > 85%, then it should be treated with angioplasty.

Guidelines for Vascular Access 1. Preferred type: AVF > AVG > Tunneled > Non-tunneled 2. Preservation of vein for fistula creation • Avoid pricking in this arm • Exercise of the hand with a squeezable ball 3. Timing: In CKD stage 4 Rule of Sixes • Vein diameter should be at least 6 mm • Less than 6 mm below the skin • Have a blood flow of at least 600 ml/min • Straight segment for cannulation that is at least 6 cm in length • Generally, maturation occurs by around 6 weeks after surgery Indication of Access Visualization Flow through a forearm AV fistula commonly averages 500–800 ml/min and in graft, flow is sometimes higher, about 1000 ml/min. Flow in upper arm fistulas or graft may be considerably higher. AV fistulas may maintain patency at flows as low as 200 ml/ min, whereas AV graft begin to clot at access flows between 600 and 800 ml/min. KDOQI recommendations are to have the patient referred for access visualization if access flow is 2.0 mm at the wrist and no calcification or segmental stenosis was detected. Also with tourniquet in place at the wrist, the cephalic vein diameter had to be at least 2.5 mm.

Short Cases

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Scenario

General Examination of Lower Limbs There are multiple purpura involving both the legs below the knee, some are red and some are dark, some are palpable, some are not and do not blanch on pressure. Differential Diagnosis (If the Patient is Child) • ITP • Henoch-Schönlein purpura (HSP) Q1. What else do you want to see if HSP? Ans. Buttock Q2. What history do you like to take in Henoch-Schönlein purpura (HSP)? Ans. Arthritis, abdominal pain, bloody diarrhea and urinary complaint (haematuria) Q3. What are the differential diagnoses? Ans. • Drug rash • ITP • SLE • Septicemia • Thrombotic thrombocytopenic purpura (TTP)

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Manual of Clinical Nephrology

Discussion Small vessel systemic vasculitis predominantly affecting children. • Peak incidence age 4–5 (range generally 2–11). • 2:1 : ratio. • Caucasian > black patients. More common in winter and early spring—associated with an upper respiratory tract infection (with accompanying fever and malaise) in 2/3. IgA plays a critical role in the pathogenesis of HSP (circulating IgA containing immune complexes, IgA deposition in vessel walls and renal mesangium). These abnormalities are associated with IgA1, not IgA2. IgA complexes and complement deposition in target organs and release of inflammatory mediators. Serum IgA elevated in 50%. A small number is ANCA-positive.

Clinical Presentation Presents as a tetrad of skin rash, abdominal pain, arthralgia, and renal involvement. Rash: Skin manifestations usually dominate the clinical picture. Purpuric (usually symmetrical) rash, affecting legs, buttocks (and, less frequently, arms). Abdomen, chest, and face are typically spared. New lesions may develop over several months. Histology: Leucocytoclastic vasculitis with vascular IgA and C3 deposition. Urticaria may also occur. Abdominal: GI manifestations in 3/4 patients. Nausea, vomiting, diarrhea (may be bloody), colicky pain (which may be severe), GI bleeding, ileus, infarction, perforation, intussusception, pancreatitis, cholecystitis. Arthralgia: Joint manifestations in 2/3 patients. Usually symmetrical polyarthralgia, mainly involving knees and ankles, wrists and fingers less common. True arthritis and permanent damage extremely rare. Renal involvement: Focal and segmental mesangial proliferative GN presenting as haematuria, proteinuria (which can be nephrotic range), renal impairment and raised BP. A renal biopsy is usually reserved for nephritic/nephrotic presentations, renal impairment, and persistent or heavy proteinuria. The severity of renal sequelae is often not related to the severity of other manifestations. Other: Pulmonary haemorrhage, cerebral vasculitis (headache, irritability, seizures, focal weakness, altered mental state), neuropathies, and orchitis. Prognosis: Usually self-limiting (usually 70 ml/min per 1.73 m2, be treated the same way as for IgAN with a 6-month course of corticosteroid.

Corticosteroid Regimens in Patients with IgAN References

Pozzi C et al.

Manno C et al.

Regimen

Intravenous bolus injections of 1 g methylprednisolone for 3 days each at months 1, 3, and 5, followed by oral steroid 0.5 mg/kg prednisone on alternate days for 6 months

6-month regime of oral prednisone starting with 0.8–1 mg/kg/d for 2 months and then reduced by 0.2 mg/ kg/d per month for the next 4 months

Treatment of crescentic HSP nephritis in children: Children with crescentic HSP with nephrotic syndrome and/or deteriorating kidney function are treated the same as for crescentic IgAN. Prevention of HSP nephritis in children: Do not use corticosteroids to prevent HSP nephritis. HSP nephritis in adults: HSP nephritis in adults be treated the same as in children.

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Scenario Instruction Look at the face or examine the face

Inspection There are multiple erythematous and scaly rashes on the face along the butterfly distribution, also involving the forehead and cheeks with clear margin. Q1. What are the differential diagnoses? Ans. • Systemic lupus erythematosus • Discoid lupus erythematosus • Dermatomyositis • Mixed connective tissue disease • Sarcoidosis • Drug rash Q2. What else do you want to examine? Ans. • Rash in the other parts of the body • Mouth ulcer • Arthropathy or arthritis • Anaemia • Proximal myopathy • Sensation over skin • History of PKDL • Drug history • Lymphadenopathy or organomegaly

Short Cases

Q3. What history do you like to take if it is SLE? Ans. • Whether the rash is aggravated on exposure to sunlight • Drug history • Repeated abortion history in female • Convulsion, depression, unconsciousness, paralysis or paresis • Raynaud phenomenon • History of DVT or thromboembolism • Family history of SLE Q4. What are the types of SLE according to ARA criteria? Ans. • Possible SLE: When 2 criteria are present • Probable SLE: When 3 criteria are present • Definite SLE: When 4 or more criteria are present • Classic SLE: When many criteria are present Q5. What are the drugs causing SLE? Ans. • Hydralazine • Procainamide • Anticonvulsant drugs • Phenothiazine • Isoniazid • Oral contraceptive pill • Ace inhibitor • Penicillamine • Methyldopa • Minocycline Q6. What are the presentations of lupus nephritis? Ans. • May be asymptomatic • Proteinuria • Hematuria • Presence of cast in urine • AKI • CKD Q7. What investigations should be done in SLE? Ans. • Urine routine and microscopy examination • CBC • Blood urea and serum creatinine • CRP • Complements • ANA

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30

• Anti-ds DNA • Anti-Smith (Sm) antibody • Antiphospholipid antibody • 24-hr urinary protein • CCR • Renal biopsy • Skin biopsy

Discussion Definitions of response to therapy LN. Complete response: Return of SCr to previous baseline, plus a decline in the uPCR to