1. How do patients with kidney disease typically present?

Patients with kidney disease typically present in several ways:

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  Abnormal blood laboratory studies (e.g., elevated blood urea nitrogen [BUN] and serum creatinine, decreased estimated glomerular filtration rate, or abnormal serum electrolyte values)

  
  
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  Asymptomatic urinary abnormalities (e.g., microscopic hematuria, proteinuria, microalbuminuria)

  
  
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  Changes in urinary frequency or problems with urination (e.g., polyuria, hematuria, nocturia, urgency)

  
  
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  New-onset hypertension

  
  
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  Worsening edema in dependent areas

  
  
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  Nonspecific symptomatologies (e.g., nausea, vomiting, malaise)

  
  
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  At times, symptoms can be specific (e.g., ipsilateral flank pain in those with obstructing nephrolithiasis)

  
  
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  Incidental discovery of anatomic kidney abnormalities on routine imaging studies (e.g., horseshoe kidney, congenitally absent or ptotic kidney, asymmetric kidneys, angiomyolipoma, kidney mass, polycystic kidneys)

  
  
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  Symptoms related to underlying systemic disease (e.g., skin changes and/or rash with scleroderma, vasculitis, systemic lupus erythematosus [SLE], arthritis due to gout, SLE, etc.)

2. What important features need to be elicited in the history of patients referred for kidney disease evaluation?

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  Previous diagnosis of kidney disease (e.g., previous documentation of BUN and serum creatinine values)

  
  
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  History of asymptomatic urinary abnormalities (e.g., hematuria, proteinuria)

  
  
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  History of alterations in urinary frequency or urgency, etc.

  
  
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  Change in the urinary character or appearance (e.g., smell, color, frothy appearance)

  
  
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  History of diabetes (duration, severity, end-organ damage)

  
  
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  History of hypertension (including cardiac history)

  
  
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  Previous exposure to nephrotoxic medications (e.g., nonsteroidal antiinflammatory drugs [NSAIDs], antibiotics such as aminoglycosides)

  
  
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  Previous adverse reactions to renin-angiotensin-aldosterone system blocking agents (e.g., angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists)

  
  
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  Recent gastrointestinal endoscopic procedures requiring bowel cleansing (risk of acute phosphate nephropathy in those who use phosphate-containing enema)

  
  
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  Recent exposure to contrast-requiring procedures (risk of contrast-induced acute kidney injury)

  
  
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  Recent systemic infections or intercurrent illnesses

  
  
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  Family history of kidney disease or any relative requiring some form of renal replacement therapy (e.g., polycystic kidney disease [PKD], Alport syndrome)

  
  
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  History of autoimmune diseases

  
  
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  Recent changes in dose of a medication, or any new medication recently started

  
  
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  Any over-the-counter medications used (e.g., NSAIDs) and/or herbal, natural supplements

3. Why is smoking history important in patients with kidney disease?

Chronic kidney disease has been shown to be closely related to cardiovascular disease and smoking. The concept of smoking as an “independent” progression factor in kidney disease has been a subject of interest in numerous investigations. Since 2003 several publications of clinical and experimental data concerning the adverse kidney effects of smoking have drawn interest, including large, prospective, population-based, observational studies. These studies clearly demonstrate that smoking is a relevant risk factor, and it does confer a significant increase in the risk for progression of kidney dysfunction (i.e., elevation of serum creatinine) regardless of the underlying cause of the kidney disease.

It has been suggested that urinary cotinine, a metabolite of nicotine, can potentially be used as an objective measure of smoking exposure. Its use has not been studied in the population with chronic kidney disease.

4. What familial diseases are characterized by kidney involvement?

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  Autosomal dominant PKD (ADPKD) (chromosomes 4 and 16)

  
  
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  Autosomal recessive PKD (linked to chromosome 6)

  
  
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  Autosomal dominant tubulointerstitial kidney disease (previously known as familial juvenile hyperuricemic nephropathy type 1, medullary cystic kidney disease type 2, and or uromodulin-associated kidney disease, linked to chromosomes 1, 16, 17)

  
  
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  Focal segmental glomerulosclerosis (linked to chromosomes 1, 9, 10, 11, 19)

  
  
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  Hypertension

  
  
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  Diabetes mellitus

  
  
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  Fabry disease

  
  
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  Alport syndrome

  
  
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  Sickle cell nephropathy

  
  
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  Familial hypercalcemic hypocalciuria

  
  
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  Cystinuria

  
  
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  HDR syndrome (syndrome of hypoparathyroidism, sensorineural hearing loss, and kidney disease; also called Barakat syndrome; mapped to chromosome 10p)

  
  
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  Liddle syndromes of apparent mineralocorticoid excess and other monogenic hypertension

  
  
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  Bartter and Gitelman syndromes

  
  
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  Congenital nephrotic syndrome (Finish and other variants, mapped to chromosomes 1, 3, 11, 19)

5. What are the common symptoms and signs that are seen in patients with advanced kidney disease?

Chronic kidney disease is usually characterized by nonspecific signs and symptoms in the earlier stages and can be detected only by an increase in serum creatinine.

Symptoms

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  Loss or decreased appetite (protein aversion)

  
  
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  Easy fatigability

  
  
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  Generalized weakness

  
  
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  Involuntary weight loss (resulting from cachexia) or gain (resulting from fluid retention)

  
  
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  Alterations in mentation (e.g., lethargy, coma, difficulty concentrating)

  
  
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  Nausea and vomiting; dyspepsia

  
  
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  Metallic taste

  
  
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  Generalized itching or pruritus

  
  
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  Seizures

  
  
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  Difficulty breathing

  
  
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  Edema

  
  
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  Intractable hiccups

  
  
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  Frothy” appearance of urine (usually results from proteinuria)

  
  
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  Decreased sexual interest (e.g., erectile dysfunction)

  
  
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  Restless legs

Signs

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  Elevated blood pressure (BP)

  
  
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  Pallor (from anemia)

  
  
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  Volume overload (jugular venous distention, peripheral edema, pulmonary edema, anasarca)

  
  
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  Friction rub (pericarditis)

  
  
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  Asterixis and myoclonus (uremic encephalopathy)

6. What is a bedside diagnostic test that will suggest the presence of underlying diabetic nephropathy?

Funduscopy. It is believed that the similarities in the vascularization between the retina and the kidneys account for the correlation of the typical microvascular complications commonly seen in patients with diabetes mellitus.

Patients with type 2 diabetes with proliferative retinopathy often present with kidney involvement, manifested by either microalbuminuria (in the earlier stages) or overt proteinuria. Therefore it is recommended that all patients with diabetes and proliferative retinopathy undergo an evaluation of kidney function including testing for microalbuminuria.

It must be remembered that although the presence of retinopathy does support a diabetic source of proteinuria, the lack of diabetic retinopathy does not rule out diabetic nephropathy.

7. What are the common extrarenal manifestations associated with kidney diseases?

Dermatologic

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  See Question 8

Arthritis and/or Musculoskeletal Symptoms

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  Lupus nephritis

  
  
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  Rheumatoid arthritis

  
  
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  Henoch-Schönlein purpura

  
  
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  Cryoglobulinemia

  
  
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  Sarcoidosis

  
  
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  Amyloidosis

  
  
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  Multiple myeloma

  
  
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  Gouty nephropathy

Hemoptysis

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  Acute kidney injury with community acquired pneumonia

  
  
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  Pulmonary renal syndrome

  
  
  
  
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    Goodpasture syndrome (also called anti-GBM disease)

    
    
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    Henoch-Schönlein purpura and immunoglobulin A nephropathy

    
    
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    Anti-Neutrophil Cytoplasmic Antibody (ANCA)-related vasculitides: Granulomatosis with polyangiitis (previously called Wegener granulomatosis); eosinophilic granulomatosis with polyangiitis (previously called Churg-Strauss syndrome); microscopic polyangiitis; and pauci-immune crescentic glomerulonephritis

    
    
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    Cryoglobulinemia

  
  
  
  
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  Lupus nephritis with pneumonitis

  
  
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  Pulmonary thromboembolism/infarction related to hypercoagulability (membranous nephropathy and antiphospholipid syndrome)

  
  
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  Volume overload (congestive heart failure, mitral stenosis)

Hearing loss

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  Hearing loss from aminoglycosides or loop diuretics in someone with kidney disease

  
  
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  Alport syndrome

  
  
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  Charcot-Marie-Tooth syndrome

  
  
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  HDR syndrome (hypoparathyroidism, sensorineural hearing loss, and kidney disease; also called Barakat syndrome)

  
  
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  Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy)

  
  
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  Bartter syndrome (type IV)

Abdominal discomfort

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  Henoch-Schönlein purpura

  
  
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  Cryoglobulinemia

  
  
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  Microscopic polyangiitis

  
  
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  ADPKD

Cervicocranial aneurysms:

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  ADPKD (also with mitral valve prolapse)

  
  
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  Fibromuscular dysplasia