„ .

Manual o f
Clinical
Nephrology
Muhammad Rafiqul Alam

V
v

C B S D e d ic a te d to E d u ca tio n
CBS P u b lish e rs & D is trib u to rs Pvtua
Manual o f
Clinical
Nephrology
Muhammad Rafiqul Alam mbbs md fcps
Professor
D epartm ent o f Nephrology
B angabandhu Sheikh Mujib M ed ica l University (BSMMU)
Dhaka, Bangladesh

CBS

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P Foreword

I t is of im m ense pleasu re for me to w rite the Forew ord to M anual o f

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
j Preface

or a long time I am being involved in fellowship examination in nephrology and

F 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

j Contents

Foreword by Matiur Rahman v

Foreword by Kanak Kanti Barua vii
Preface ix

1. Short Cases______________________________________________________ 1

2. Structured Clinical Assessment (SCA)________________________ _ _ 37

3. Instrument and Specimen__________________________________ _ _ 65

4. Radiology and Imaging-----------------------------------------------------------------79

5. Transplant Work Up--------------------------------------------------------------------- 92

Index 101
 Short Cases,

Scenario

Q l. 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.
 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, derma-
tomyositis, 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.
Q ll. 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.
 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.
Q l. 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
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

Q5. How will you monitor drug level?

• For cyclosporine: C2 level (2-hour post dose)/CO (12-hour trough)
• For tacrolimus: CO 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

U rin e o u tp u t T yp e and s e q u e n c e o f IV f lu id in fu s io n

100 m l/hr Add 50 ml to output DA/NS/DA/NS

1 0 0 -3 0 0 ml/hr Add 25 ml to output D A/N S/D A/N S/H S

3 0 0 -5 0 0 ml/hr Give exact am ount of output DA/N S/H S

> 500 m l/hr Give 50 ml less to the output D A/H S/N S/H S
*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.
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

B 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

P ro p h y la x is R e g im e n C o m m e n ts

P n e u m o c y s tis F ir s t lin e : TM P-SM X x 6 months TM P-SM X also reduces the incidence

jiro v e c ii S e c o n d lin e (sulphur allergies): of To xoplasm a go n d ii, L is te ria m o n o c y ­
Atovaquone, dapsone or aerosolized tog ene s, a n d N o c a rd ia a s te ro id s a n d
pentam idine reduces the incidence of UTI in kidney
transplant recipients.

Fungal Nystatin S & S (x 1 month) or Fluconazole recommended in high-risk

fluconazole (x 3 - 6 months) recipients (e.g. com bined liver-kidney
o r p a n c re a s -k id n e y tra n sp la n t re ci­
pients, history of coccidioidom ycosis,
patients who live in endem ic areas)

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