Examination Medicine: A Guide to Physician Training, 7th Edition

CHAPTER 11. The renal long case

When the patient dies the kidneys may go to the pathologist, but while he lives the urine is ours.

Thomas Addis (1881–1949)

Chronic kidney disease (chronic renal failure)

Chronic kidney disease (CKD) by itself is not a particularly common subject for the long case. However, it is a difficult and important topic and kidney disease is often present in that very common long case, the obese diabetic with hypertension and vascular disease. Keep in mind the current CKD classification (Table 11.1). The patient will usually know that he or she has renal disease. Methodical questioning to establish the diagnosis, cause, management and complications is necessary.

Table 11.1

Stages of chronic kidney disease

STAGE

DESCRIPTION

GFR (ML/MINUTE)

1

Kidney damage but normal GFR

>90

2

Kidney damage and mild GFR reduction

60–89

3

Moderate reduction in GFR

30–59

4

Severe reduction in GFR

15–29

5

Kidney failure

<15

GFR = glomerular filtration rate.

The history

QUESTIONS REGARDING SYMPTOMS, DIAGNOSIS AND AETIOLOGY

1. The earliest symptoms of renal failure include nocturia, lethargy and loss of appetite. Patients are sometimes diagnosed following an episode of haematuria or loin pain. The first episode of overt renal failure may have been precipitated by a further insult, such as use of NSAIDs, radiocontrast injections, infection, ACE inhibitors or AR blockers (if bilateral renal artery stenosis), dehydration or anaemia. Asymptomatic proteinuria or haematuria may have been detected during a routine or insurance medical examination or during pregnancy.

2. Glomerulonephritis (Tables 11.2 and 11.3). Determine whether there is a history of proteinuria, haematuria, oliguria, oedema, sore throat, sepsis, rash, haemoptysis or renal biopsy. Ascertain treatment details (e.g. antihypertensives, immunosuppressives, anti-platelet therapy, dialysis).

Table 11.2

The nephrotic syndrome

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Note: Renal vein thrombosis is a complication and rarely a cause of the nephrotic syndrome.

Table 11.3

Classification of glomerulonephritis

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2. Diabetic nephropathy. Ask about other complications and therapy. An ACE inhibitor or AR blocker is preferred for all cases with diabetic nephropathy.

3. Polycystic kidneys. Ask about family history, how the disease was diagnosed, haematuria, polyuria, loin pain, hypertension, renal calculi, headache, subarachnoid haemorrhages and visual disturbance (intracranial aneurysm). Also ask about deafness and a history of persistent haematuria (hereditary nephritis – Alport’s syndrome).

4. Reflux nephropathy. Ask about childhood renal infections, cystoscopy, operations, treatment (e.g. regular antibiotics) and enuresis.

5. Analgesic nephropathy. Ask about the number, type and duration of analgesics consumed, urinary tract infections, hypertension, haematuria, gastrointestinal blood loss, nocturia, renal colic (sloughed papillae, stones), transitional cell cancer and anaemia. This cause of renal failure is now very uncommon following the withdrawal of compound analgesics containing aspirin and phenacetin, but some of these patients are still available (alive).

6. Hypertensive nephropathy. Ask how the disease was diagnosed, duration and control of hypertension, treatment and compliance with medication, angiography, family history.

7. Connective tissue disease. Think especially of systemic lupus erythematosus and scleroderma.

8. Find out whether the patient is aware of the long-term prognosis. If he or she is not on dialysis yet, has this been discussed? Is the patient likely to be eligible for dialysis or the transplant list?

9. Ask when the underlying condition was diagnosed and how it is being treated. The progression to end-stage kidney disease may be rapid or very prolonged.

QUESTIONS REGARDING MANAGEMENT (Table 11.4)

Table 11.4

Principles of management of CKD

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1. Conservative management

a. Ask about follow-up, medications, diet, salt and water allowance, investigations performed (particularly renal biopsy) and whether erythropoietin has been given subcutaneously in an attempt to elevate the haemoglobin.

b. Has the patient been advised to restrict protein intake? There is controversy about the value of protein restriction in delaying end-stage renal failure. Patients with nephrotic syndrome should be much less restricted. The concern about protein restriction is that it leads to more rapid loss of muscle mass without much delay in end-stage renal failure.

c. What effect have the disease and the dietary and other restrictions had on the patient’s quality of life and his or her family?

d. Certain treatments can slow the progression of glomerulonephritis to end stage renal failure. Ask about specific treatment including steroids and other immunosuppressants, treatment of hypertension and advice about smoking cessation and avoidance of nephrotoxins.

2. Dialysis (Table 11.5). Ask about haemodialysis or peritoneal dialysis, including where performed, how often, how many hours per week, relief of symptoms with treatment and subsequent complications. Also ask about shunts, other operations (e.g. renal tract operations, parathyroidectomy) and medications taken.

Table 11.5

Dialysis

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Note: Mortality from dialysis is caused by myocardial infarction (60%) or sepsis (20%) in most cases. Acquired cystic disease in native kidneys may occur; <5% are malignant. Arthropathy and carpal tunnel syndrome may occur in long-term dialysis patients owing to amyloid (beta2-microglobulin) deposition.

APD = automated peritoneal dialysis (exchanges done at night); CAPD = chronic ambulatory peritoneal dialysis.

3. Transplant work-up and management. Ask when and how many, whether living relative or cadaver, postoperative course, improvement, symptoms since transplantation, medications, follow-up and long-term complications (e.g. neoplasia, steroid complications).

4. Bladder management for reflux or neurogenic bladder.

5. Social arrangements and ADLs. Ask about employment, the family’s ability to cope, travel, sexual function and financial situation.

QUESTIONS REGARDING COMPLICATIONS

1. Conservatively treated patients. Ask about symptoms of anaemia, bone disease, secondary gout or pseudo gout, pericarditis, hypertension, cardiac failure, fluid overload, peripheral neuropathy, pruritus, peptic ulcers, impaired cognitive function and poor nutrition. Have the doses of renally excreted drugs given for other conditions been reduced? Remember that although most drugs that require a loading dose are begun at their usual dose (and then continued at a reduced maintenance dose), digoxin, which has an altered volume distribution, must have its loading dose reduced.

2. Dialysis patients. Ask about shunt blockage and access problems, infection, pericarditis, peritonitis, etc.

3. Transplant patients. For patients with recent transplants ask about graft pain or swelling (failure of graft function, rejection), infection, urine leaks and steroid side-effects. For those with long-term renal grafts, ask about serum creatinine levels, proteinuria, recurrent glomerulonephritis (dense deposit disease), avascular necrosis, skin cancer and reflux nephropathy. Find out about compliance with drugs and whether the patient knows about rejection episodes and treatment (e.g. with muromonab–CD3).

The examination (see Table 11.6)

A complete physical examination is always essential. Look particularly for the following.

Table 11.6

Chronic kidney disease (renal failure)

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1. General appearance – mental state, hyperventilation, Kussmaul’s breathing, hiccupping and the state of hydration.

2. Hands – nails for white transverse opaque bands or lines in hypoalbuminaemia; a brown arc near the ends of the nails (Terry’s nails – see Fig 11.1) in renal failure. Also palmar crease pallor, vasculitis, vascular shunts at the wrist, scars from old vascular access sites, asterixis and peripheral neuropathy.

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FIGURE 11.1 Terry’s nails in chronic kidney disease. There is proximal pallor with distal brownish color in a patient with chronic renal failure. G M White, N H Cox (eds). Diseases of the skin: A color atlas and text, 2nd edn. St. Louis, Mosby, Elsevier, 2006, with permission.

3. Arms – bruising, pigmentation, scratch marks, subcutaneous calcification, myopathy, fistulae and skin cancers, especially squamous cell carcinomas.

4. Face – eyes for jaundice, anaemia and band keratopathy (caused by hypercalcaemia); mouth (dry, fetor); rash (e.g. SLE); and a Cushingoid appearance.

5. Chest – pericardial rub, cardiac failure, lung infection, pleural effusion and venous hum (shunt). Presence of central venous catheter for access to dialysis.

6. Abdomen – palpable kidney, scars (owing to dialysis or transplants), renal artery bruit (a systolic bruit, or occasionally a systolic–diastolic bruit in the upper abdomen, suggests possible renal artery stenosis), bladder enlargement, rectal examination (for prostatomegaly, urethral mass and signs of blood loss), nodes (lymphoma, cytomegalovirus or other infections if the patient is immunosuppressed), ascites (dialysis or other causes), and femoral bruits and pulses.

7. Urine – for blood, protein, specific gravity, pH, glucose, urine microscopy and examination of the urinary sediment for casts.

8. Legs – oedema, bruising, pigmentation, scratch marks, peripheral neuropathy, vascular access and myopathy.

9. Back – bone tenderness and sacral oedema.

10. Blood pressure lying and standing. Fundoscopy.

Investigations

1. Determine renal function:

a. glomerular filtration rate (GFR) – creatinine clearance (creatinine clearance levels of <10 mL/min are considered indications for dialysis) and plasma creatinine/urea level; the GFR is routinely calculated by laboratories and the patient may know these results

b. tubular function – plasma electrolyte levels, urine specific gravity and pH, glycosuria, serum phosphate and uric acid, aminoaciduria, serum calcium and plasma albumin levels

c. urine analysis and urinary protein excretion (protein-to-creatinine ratio)

d. others if necessary – CT scan for renal artery stenosis or urinary tract obstruction.

2. Determine renal structure:

a. ultrasound – renal size and symmetry, signs of obstruction; small kidneys suggest chronic disease

b. plain X-ray film of the abdomen (KUB – kidneys, ureters, bladder)

c. intravenous pyelogram (IVP) under good hydration (but avoid in patients with diabetes mellitus or myeloma, or when the creatinine level is >150 mmol/L – it has largely been replaced by less invasive tests)

d. CT scan – same restrictions as for IVP if contrast is to be used; hydration with IV saline does offer some renal protection; the use of oral N-acetylcysteine before and after the use of contrast material is of uncertain benefit

e. cystoscopy and retrograde pyelography

f. other – renal artery Doppler study, CT renal angiography.

3. Consider investigations aimed at assessing the widespread effects of renal failure – blood count; serum ferritin and iron saturation level; midstream urine examination; calcium, phosphate and alkaline phosphatase levels; parathyroid hormone level; nerve conduction studies; arterial Doppler studies.

4. Decide whether there are features that favour chronic over acute kidney disease: nocturia, polyuria, longstanding hypertension, renal osteodystrophy, peripheral neuropathy, anaemia, hyperphosphataemia and hyperuricaemia. The differentiation of acute and chronic renal failure is also aided by determining kidney size. They are usually small in chronic kidney disease, but the exceptions to this rule include:

• diabetic nephropathy (early)

• polycystic kidneys

• obstructive uropathy

• acute renal vein thrombosis

• amyloidosis

• rarely other infiltrative diseases (e.g. lymphoma), which can all produce chronic renal failure but maintain normal kidney size.

In general, however, kidneys enlarge or maintain normal size in acute renal failure and are small in chronic renal failure.

5. Look for anaemia and the presence of burr cells in the peripheral blood film, which are usually indicative of chronic kidney disease but may occur in acute renal failure (e.g. in SLE), thrombotic thrombocytopenic purpura and the haemolytic uraemic syndrome.

6. Always ask about previous urine analyses, such as insurance examinations, in which proteinuria may have been detected and followed up, thus giving a clue about chronic glomerulonephritis.

7. Consider investigations aimed towards the likely underlying disease process – measurement of antinuclear antibody; hepatitis B surface antigen; hepatitis C; HIV; complement; immune complexes; immunoelectrophoresis; micturating cystogram; urine cytology; renal biopsy.

Treatment

This most chronic disease (see Table 11.7) has profound effects on the patient and his or her relatives. The association between the patient and the renal physician and nursing staff becomes a very intense one, often lasting many years. It is important to ask detailed questions about the way the patient copes with the condition, whether work and travel are possible, and what the patient feels about the long-term prospects. Also ask whether a dialysis patient has considered accepting a kidney from a live donor.

Table 11.7

Complications and treatment of chronic kidney disease

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1. Treat reversible causes of deterioration. These include:

a. hypertension

b. urinary tract infection

c. urinary tract obstruction

d. dehydration

e. cardiac failure

f. drug use (e.g. radiocontrast, NSAIDs, aminoglycosides, cyclosporin)

g. hypercalcaemia

h. hyperuricaemia with urate obstruction

i. hypothyroidism or rarely hypoadrenalism.

2. Monitor and control the blood pressure very carefully. Treat lipids.

3. Carefully attend to salt and water balance and acidosis.

4. Normalise the calcium and phosphate levels with diet, phosphate binders or calcitriol.

5. Restrict dietary protein. Although this may delay slightly the need for dialysis, it leads to wasting and protein malnutrition. It is no longer universally recommended.

6. Assess and treat sexual dysfunction.

7. Dialyse when indicated (see below).

8. Consider transplantation.

The absolute indications for dialysis are (see Table 11.5):

1. uraemic symptoms despite conservative management (eGFR about 7 mL/min)

2. volume overload despite salt and water restriction and diuretic use

3. hyperkalaemia unresponsive to conservative measures

4. progressive deterioration of renal function (dialyse before symptoms develop)

5. acute renal failure (dialyse early).

Note: Dialysis may be started earlier to avoid these complications.

Renal transplantation

Renal transplantation is now a widely accepted, commonly performed treatment for end-stage renal failure. Unfortunately patients continue to have a number of chronic problems that may bring them into hospital and make them available for examinations. Cadaveric transplantation is generally more common than the use of matched family donors. Specific contraindications to renal transplantation include recent malignancy, an untreatable focus of infection and severe external disease.

The prognosis continues to improve and the introduction of cyclosporin and other immunosuppressives has made a substantial difference to survival rates. The 1-year graft survival rate is now more than 90% in experienced centres. The selection of patients for transplant is difficult. Shortages of donor organs mean that transplant is not offered to elderly patients, those with other serious illnesses or those with unrevascularised coronary artery disease.

The history

1. Ask the patient about the cause of the original renal failure. Find out how long the transplant has been in situ and whether this is the patient’s first transplant. Ask whether the kidney came from a relative or was a cadaveric graft.

2. The patient should be well informed about previous rejection episodes and how these have been managed. Find out whether this is the reason for the current admission. Clinically, rejection may be marked by fever, swelling and tenderness over the graft. The patient should be aware of all these signs. There is also often a reduction in urine volume. A rise in creatinine level is usual. Ask about recent graft biopsies, which may have been necessary to assess rejection, recurrence of disease or drug toxicity.

3. Find out what immunosuppressive drugs the patient is taking and in what doses. He or she should know whether changes in doses have been required recently because of problems with any of the drugs.

4. Ask about specific complications of immunosuppression.

a. Cyclosporin can result in significant side-effects. The drug can be associated with an increase in hirsutism, tremor, gout, renal impairment, increased liver function tests (especially bilirubin), hypertension, hyperkalaemia, hypomagnesaemia, gingival hypertrophy and rarely haematological malignancy.

b. Mycophenalate is associated with an increased risk of infections and leukopenia.

c. The mTOR inhibitors sirolimus and everolimus are associated with proteinuria, hyperlipidaemia, pneumonitis, tendon rupture and slow wound healing. They may need to be stopped temporarily before and after surgery.

d. Ask about ischaemic heart disease and peripheral vascular disease, infections and malignancy, as the incidence of these conditions remains higher than in the general population.

The examination

1. Look particularly at the skin for squamous and basal cell carcinomas.

2. Note any signs of Cushing’s syndrome and hirsutism (e.g. cyclosporin).

3. Examine the abdomen carefully, noting the position and site of the allograft and whether it has any tenderness or bruits.

4. Look for old vascular access sites for haemodialysis and decide whether there will be problems finding sites for access for further dialysis if this is required.

5. Examine the lungs for signs of infection and the mouth for Candida. Inspect the gums. Note gouty tophi. Look at the temperature chart.

Investigations

1. It is important to obtain the serum creatinine level and, if possible, establish whether the serum creatinine level has been rising or falling since the time of transplantation. A slightly elevated creatinine level is considered acceptable in patients on cyclosporin treatment as this drug interferes with renal function. Patients usually know their creatinine and eGFR results. If they don’t, there may be some doubt about their compliance with treatment and understanding of their disease.

2. The electrolyte levels and liver function test results are important. Cyclosporin can cause hepatotoxicity and renal impairment, as can cytomegalovirus infection of the liver.

3. A white cell count should be obtained to look for leucocytosis (infection or steroids) and leucopenia (e.g. excessive doses of azathioprine). The azathioprine dose is usually adjusted according to the neutrophil count. The haemoglobin is usually normal in patients with a successful transplant and good function.

4. The results of blood cultures should be sought if there has been any suggestion of recent infection. Urinary tract infection must also be considered and early urine microscopy is helpful.

5. Exclude prerenal and postrenal disease. A renal scan and ultrasound with measurement by Doppler is useful for estimating renal artery blood flow.

Management

1. The majority of patients receiving chronic dialysis are candidates for renal transplantation (Table 11.8). The donor’s kidneys should be ABO-compatible. Typing by human leucocyte antigens (HLA) -A, -B and -DR improves graft survival. Three HLA antigens are inherited from each parent. A complete match is for six antigens. The graft survival rate for these patients is 50% at 20 years. The long-term graft survival rate declines with a decrease in the number of matches. The recipient is usually screened for antibodies to class 1 antigens (HLA-A and -B) before receiving the transplant, as their presence is associated with hyperacute rejection.

Table 11.8

Contraindications to renal transplant

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2. Management problems include acute tubular necrosis, infection, cyclosporin nephrotoxicity (acute vasoconstriction, haemolytic uraemic syndrome or dose-related nephrotoxicity) rejection episodes, disease recurrence and chronic allograft nephropathy.

3. Rejection is prevented by the use of steroids, mycophenolate and calcineurin inhibitors (usually tacrolimus 100–150 mg twice daily) or mTOR (mammalian target of rapamycin) inhibitors (everolimus and sirolimus).

a. Mycophenalate can be used with allopurinol, can cause leukopenia, its dose is 500 mg–1000 mg twice daily.

b. Tacrolimus is a calcinerurin inhibitor. Trough levels should be monitored (5–10 ng/mL). It can cause renal dysfunction, alopecia and hypertension but (unlike cyclosporin) not gout, hirsutism or gum changes.

c. Sirolimus and Everolimus are mTOR inhibitors, given daily orally. Their adverse effects include a reduced white cell count (use with caution in combination with mycophenalate), increased lipids and proteinuria. Monitor trough levels. They delay wound healing and should be replaced before surgery with tacrolimus and restarted 1–3 months later.

Acute rejection episodes are treated with three pulse doses of 0.5–1 g intravenous methylprednisolone or monoclonal antibody (e.g. muromonab–CD3) if the episode is resistant to steroids. Azathioprine is given in doses of 1.5–3 mg/kg/day; it is metabolised by the liver so its dose does not need to be varied according to renal function, but the dose is usually adjusted according to the neutrophil count. The use of allopurinol should be avoided because it interferes with azathioprine excretion and increases bone marrow toxicity.

Azathioprine has largely been replaced by mycophenalate (resulting in less acute rejection), but some patients with older transplants may still be taking azathioprine.

Prednisone is given in maintenance doses of approximately 7.5–10 mg daily after about 6 months. A gradually rising creatinine level may be a sign of cyclosporin toxicity (which, if caused by interstitial fibrosis, is not reversible) or of chronic rejection. This is a difficult clinical problem, but graft biopsy can be used to decide whether the cyclosporin should be stopped or immunosuppression increased.

4. Opportunistic infections typically occur a month or more post-transplant. ToxoplasmaNocardia and Aspergillus are now less common with current immunosuppressive protocols; viral infections (especially CMV) dominate. Infection must be aggressively diagnosed (e.g. by blood cultures and lung biopsy) and treated. When infections are life-threatening, immunosuppressive treatment, apart from prednisone, should be suspended. CMV prophylaxis with ganciclovir and PCP prohylaxis with co-trimoxazole may be indicated.

5. The major cause of graft loss is chronic rejection (chronic allograft nephropathy).

6. Recurrence of glomerulonephritis in the transplanted kidney is not uncommon but is an uncommon cause of loss of the transplant. It is most common with focal glomerulosclerosis. IgA nephropathy, Goodpasture’s syndrome but membranoproliferative glomerulonephritis (especially type II) can also recur.

7. Some diabetic patients with end stage renal failure will have undergone kidney/pancreas transplants. They may have the additional problems with pancreatic drainage (bladder or to gut) and leakage.