Renal Disorders
M. Rabie Al-Turkmani
INTRODUCTIONThis chapter provides the latest information on diagnosis of common renal disorders. It also reviews congenital disorders and tumors of the kidney as well as renal involvement in selected diseases. Each entry is organized with a brief definition of the disorder, information regarding clinical presentation, and
laboratory findings. Infectious renal and urinary tract diseases are discussed elsewhere in this book (see Chapter 9, Genitourinary System Disorders, and Chapter 13, Infectious Diseases).
laboratory findings. Infectious renal and urinary tract diseases are discussed elsewhere in this book (see Chapter 9, Genitourinary System Disorders, and Chapter 13, Infectious Diseases).
ACUTE KIDNEY INJURY (ACUTE RENAL FAILURE)
□ Definition
Acute kidney injury (AKI), previously known as acute renal failure (ARF), is characterized by a rapid decline in kidney function that limits its ability to maintain homeostasis and eliminate nitrogenous waste. AKI is found in 7% of all hospitalized patients and up to 30% of critically ill patients.
AKI is defined as any of the following:
▼ Increase in serum creatinine by ≥0.3 mg/dL within 48 hours
▼ Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days
▼ Urine volume of <0.5 mL/kg/hour for 6 hours
According to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, AKI is classified in three stages:
▼ Stage 1: increase in serum creatinine to 1.5-1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL (≥26.5 µmol/L), or reduction in urine output to <0.5 mL/kg/hour for 6-12 hours
▼ Stage 2: increase in serum creatinine to 2.0-2.9 times baseline, or reduction in urine output to <0.5 mL/kg/hour for ≥12 hours
▼ Stage 3: increase in serum creatinine to 3.0 times baseline, or increase in serum creatinine to ≥4.0 mg/dL (≥353.6 µmol/L), or the initiation of renal replacement therapy, or anuria for ≥12 hours, or in patients <18 years, decrease in estimated glomerular filtration rate (GFR) to <35 mL/minute/1.73 m2
Causes of AKI can be divided into three categories:
▼ Prerenal: hypovolemia (e.g., hemorrhage, dehydration, burns), anaphylactic or septic shock, heart failure, or decreased renal perfusion due to drugs or toxins
▼ Renal (intrinsic): acute tubular necrosis (ATN) due to renal ischemia, nephrotoxic drugs or toxins, or acute renal diseases (e.g., acute glomerulonephritis [GN], pyelonephritis)
▼ Postrenal: due to obstruction of the urinary flow
□ Who Should Be Suspected?
Patients with AKI present in a variety of ways:
Patients with symptoms suggestive of uremia. The term uremia describes the clinical syndrome associated with retention of the end products of nitrogen metabolism due to severe reduction in renal function. It can be a consequence of either acute or chronic renal disease.
Patients with oliguria (urine output of <500 mL/day) or anuria (urine output <100 mL/day).
Patients with an elevated serum creatinine level.
Hospitalized patients with severe losses of extracellular fluid or patients exposed to nephrotoxic drugs, sepsis, or radiographic contrast agents who demonstrate the symptoms or findings described above.
□ Laboratory Findings
Urinalysis is the most important noninvasive test in the diagnosis of AKI and its etiology (see Figure 14-1). Microscopic examination is normal in most cases of prerenal disease. The presence of RBC casts or dysmorphic RBCs indicates glomerular disease, whereas the presence of cellular debris or granular casts suggests ischemic or nephrotoxic AKI. Urine specific gravity is of limited value in establishing the etiology of AKI.
Figure 14-1. Algorithm for the diagnosis of acute kidney injury.
GFR gives an approximate estimation of the number of functioning nephrons and may be markedly reduced in patients with AKI. Estimation of GFR has a prognostic rather than diagnostic utility in AKI.
Serum creatinine level is elevated at diagnosis and continues to rise. The rate of rise may be helpful in determining the etiology of AKI.
Blood urea nitrogen (BUN)/serum creatinine ratio is normal in intrinsic renal disease (10-15:1) and elevated (>20:1) in prerenal azotemia.
Urine-to-serum creatinine ratio is high in patients with prerenal disease and low with renal causes of AKI.
Patients with postrenal disease are diagnosed based on clinical presentation and imaging studies.
Several protein biomarkers have been found to signal AKI prior to the rise in serum creatinine. These candidate biomarkers include, but not limited to, kidney injury molecule-I (KIM-1), N-acetyl-β-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein, and interleukin (IL)-18.
Suggested Reading
Thomas ME, Blaine C, Dawnay A, et al. The definition of acute kidney injury and its use in practice. Kidney Int. 2015;87:62-73.
ACUTE TUBULAR NECROSIS
□ Definition
□ Who Should Be Suspected?
Candidates for investigation include patients (in most cases hospitalized) with exposure to a nephrotoxin (e.g., therapy with aminoglycoside or amphotericin B, radiologic contrast materials, heavy metals, cisplatin, ethylene glycol, or heme pigments such as free hemoglobin or myoglobin), severe trauma, hemorrhage, hypotension, surgery or sepsis, and recent-onset oliguria or anuria.
□ Laboratory Findings
Urinalysis: sloughed renal tubular epithelial cells with muddy brown epithelial and granular casts. Hyaline casts may be seen. Urine volume is typically, but not invariably, low.
Urine osmolality is typically below 400 mOsm/kg.
Fractional excretion of sodium (FENa) is an accurate test to differentiate between prerenal disease (<1%) and ATN (>1%). There are few limitations, however, to the use of FENa in determining the cause of AKI since it may be <1% in some ATN cases (e.g., when ATN is associated with a
chronic prerenal disease such as heart failure), or >1% in some prerenal disease cases (e.g., patients treated with diuretics).
Sudden elevation in serum creatinine with normal BUN/creatinine ratio (10-15:1).
CHRONIC KIDNEY DISEASE
□ Definition
Chronic kidney disease (CKD) occurs when there is a progressive, irreversible alteration in kidney structure and function, as reflected by a gradual decrease in GFR and increase in BUN and creatinine, and/or albuminuria. This condition becomes more prevalent with increasing age.
CKD is defined by the Kidney Disease Outcomes Quality Initiative (KDOQI) as:
▼ Kidney damage for ≥3 months as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by either pathologic abnormalities or markers of kidney damage
▼ GFR < 60 mL/minute/1.73 m2 for ≥3 months, with or without kidney damage
Staging of the CKD is based on the cause of disease (C), six categories of GFR (G), and three categories of albuminuria (A), collectively referred to as “CGA staging.” See Figure 14-2.
Figure 14-2. Prognosis of CKD by GFR and albuminuria category. Green, low risk (if no other markers of kidney disease, no CKD); yellow, moderately increased risk; orange, high risk; red, very high risk. CKD, chronic kidney disease; GFR, glomerular filtration rate. (From Andrassy KM. KDIGO 2012 Clinical Practice Guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;84(3):622-623.)
CKD is usually asymptomatic in its early stages (1-3). Symptoms and metabolic complications (e.g., anemia, hyperparathyroidism, water and electrolyte imbalance) usually appear at later stages when GFR drops below 30 mL/minute/1.73 m2.
The distinction between acute, subacute, and CKD is not always well defined but may be important, since AKI may be reversible, whereas CKD is not. A reduced size of the kidney (demonstrated by ultrasound) indicates a chronic phase.
The majority of CKD cases are due to glomerular disease, tubular or interstitial disease, or long-standing obstructive uropathy.
□ Who Should Be Suspected?
Patients who have had acute renal injury or GN
Patients with diseases that can initiate or propagate kidney disease, such as diabetes or hypertension
Those in whom symptoms develop insidiously suggesting uremia (easy fatigability, anorexia, vomiting, mental status changes, seizures) or generalized edema
Those in whom renal function or urinalysis abnormalities are discovered incidentally
Those with a family history of CKD or who have a congenital renal abnormality
□ Laboratory Findings
Laboratory studies are indicated once renal disease is suspected. Until renal insufficiency is severe, adaptation of tubular function allows excretion of relatively normal amounts of water and sodium.
Serum creatinine and BUN increase in parallel.
Creatinine clearance, established via well-accepted formulas, is used to estimate the GFR (estimated GFR or eGFR). This parameter is generally considered the best index of overall kidney function, and repeated determinations, in conjunction with creatinine measurement, establish whether the patient has stable or progressive disease. GFR has no etiologic diagnostic value.
Albuminuria is a marker of kidney damage that is commonly determined by measuring albumin/creatinine ratio (ACR) in untimed “spot” urine. An ACR cutoff of 30 mg/g indicates abnormality and should be repeated on at least two further occasions. Patients with two or more positive tests on early morning samples 1-2 weeks apart should be diagnosed as having persistent albuminuria.
Urinalysis
▼ Microscopic examination is an important tool in determining the etiology of CKD. WBCs, RBCs, and casts are usually found.
▼ Dipstick examinations for albumin, glucose, pH, nitrate, and blood contribute to determining the etiology of CKD.
Blood pH measurement can be helpful since acidosis is a frequent complication of advanced CKD.
Serum abnormalities include hyperphosphatemia, hyperkalemia, hyponatremia, hypocalcemia, and hypermagnesemia. Uric acid and amylase may also be increased.
Hypoalbuminemia and hyperlipidemia (increased triglycerides, cholesterol, and VLDL lipoprotein levels) may occur, and they are common in the nephrotic syndrome. Hypergammaglobulinemia with monoclonal gammopathy suggests myeloma kidney as the etiology of CKD.
Anemia, typically normocytic, normochromic, is caused by reduction in the synthesis of erythropoietin and usually develops with reduction of renal function to 30-50% of normal.
Coagulation studies may be affected by uremic by-products such as guanidinosuccinic acid and exuberant production of nitrous oxide by uremic vessels, resulting in abnormal platelet function.
Suggested Reading
Webster AC, Nagler EV, Morton RL, et al. Chronic kidney disease. Lancet. 2017;389:1238-1252.
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
□ Definition
Focal segmental glomerulosclerosis (FSGS) is a histologic lesion that is commonly found to underlie the nephrotic syndrome. It accounts for 20% of nephrotic syndrome cases in children and 40% of such cases in adults. In addition, it is the most common pathology identified in patients with ESRD.
This is classified as:
▼ Primary (idiopathic): commonly presents with nephrotic syndrome and accounts for approximately 80% of FSGS cases.
□ Laboratory Findings
Marked proteinuria; nephrotic range (>3.5 g/day) in primary FSGS and nonnephrotic in secondary FSGS.
Hypoalbuminemia (more common in primary FSGS).
Hypercholesterolemia and peripheral edema can occur.
Hematuria, microscopic and macroscopic.
Serum level of soluble urokinase receptor is elevated.
Histologic findings confirm the diagnosis.
GLOMERULONEPHRITIS
□ Definition and Classification
GN is a renal disease characterized by inflammation of the glomeruli and hematuria. It can be acute or chronic and is often associated with decreased GFR, proteinuria, edema, hypertension, and sometimes oliguria.
▼ Acute GN is defined as the sudden onset of hematuria, proteinuria, and RBC casts.
▼ Chronic GN can develop over years and, in a subset of patients, can ultimately lead to renal failure.
GN disorders can be grouped into nonproliferative and proliferative types.
Nonproliferative GN disorders include:
▼ Focal segmented glomerulosclerosis
▼ Membranous glomerulopathy
▼ Minimal change disease
Proliferative GN disorders include
▼ IgA nephropathy
▼ Postinfectious GN (PIGN)
▼ Membranoproliferative GN (MPGN)
▼ Rapidly progressive GN (RPGN)
GN can be a primary disorder due to causes intrinsic to the kidney or secondary to autoimmune disorders, infections, diabetes, or drug treatment.
Conditions associated with GN can be also classified as antibody-mediated or cell-mediated, infectious or noninfectious, or hypocomplementemic or normocomplementemic.
Antibody Mediated
For example, anti-glomerular basement membrane (GBM) disease (Goodpasture syndrome), following renal transplantation
Cell Mediated
Examples include Wegener granulomatosis and polyarteritis.
Infectious
Acute poststreptococcal (group A beta-hemolytic GN)
Hypocomplementemic
Normocomplementemic
Intrinsic renal diseases (e.g., IgA nephropathy, idiopathic RPGN)
Systemic (e.g., polyarteritis nodosa, Wegener granulomatosis)
□ Various Clinical Courses of GN
The clinical spectrum of GN comprises:
Asymptomatic subnephrotic proteinuria without hematuria.
Asymptomatic proteinuria with hematuria: the coexistence of asymptomatic proteinuria and hematuria substantially increases the risk of significant glomerular damage, hypertension, and progressive renal dysfunction in comparison with the situation of isolated asymptomatic proteinuria.
Nephrotic syndrome: proteinuria in excess of 3.5 g in 24 hours, accompanied by edema, hypoalbuminemia, hyperlipidemia, and lipiduria.
Nephritic syndrome: nonnephrotic proteinuria, hematuria, and appearing tendency to GFR lowering.
Macroscopic hematuria associated with glomerular diseases, appearing mainly in children and young adults as a symptom of IgA nephropathy and PIGN. The characteristic feature of IgA nephropathy is episodic frank hematuria occurring simultaneously with an upper respiratory tract infection, whereas in PIGN, there is a 2- to 3-week period of latency between infection and hematuria.
See Figure 14-3.
 Figure 14-3. Algorithm for evaluation of glomerulonephritis. |
GLOMERULONEPHRITIS, MEMBRANOPROLIFERATIVE
□ Definition
MPGN accounts for approximately 10% of all cases of biopsy-confirmed GN and ranks as the third leading cause of end-stage renal disease among the primary glomerulonephritides.
MPGN can be primary or secondary to systemic diseases (e.g., SLE), neoplasms, monoclonal gammopathy, or infections (especially HCV with cryoglobulinemia).
MPGN most commonly presents in childhood but can occur at any age. Patients can present with a variety of findings ranging from microscopic hematuria to severe GN associated with hypertension and nephrotic syndrome. The clinical course may be clinically active, or there may be periods of remission. Approximately 50% of untreated patients have chronic renal insufficiency in 10 years.
On the basis of the electron microscopical findings, MPGN is traditionally classified as type I (idiopathic, most common), type II, or type III (rare). In another classification that is more useful and based on the pathogenetic process, MPGN can be classified as immune complex mediated, complement mediated, or MPGN without immunoglobulin or complement deposition.
□ Laboratory Findings
Variable degree of proteinuria, which can be marked or reach the nephrotic range.
Hematuria is present in patients with active disease.
Decreased serum levels of complement C3. C4 may be normal or decreased. Clinical course is not related to serum complement levels.
GFR < 80 mL/minute/1.73 m2 in approximately two thirds of patients.
Relevant tests for the detection of secondary causes may be helpful (e.g., serologic testing and culture to detect infections, anti-GBM antibodies, cryoglobulins, serum protein electrophoresis and immunofixation, and antinuclear antibody testing).
GLOMERULONEPHRITIS, MEMBRANOUS
□ Definition
Membranous GN is an antibody-mediated disorder in which immune complexes localize between the outer aspect of GBM and epithelial cells. These complexes are formed by binding of antibodies to antigens that are part of the basement membrane or deposited from elsewhere by the systemic circulation.
It usually occurs in adults and is the second most common cause of nephrotic syndrome.
It may be primary (≥75% of cases) or secondary. Secondary membranous GN may be due to autoimmune diseases (e.g., SLE), infections (e.g., HBV, syphilis, malaria, schistosomiasis, leprosy), drugs (e.g., NSAIDs,
penicillamine), or neoplasms (e.g., non-Hodgkin lymphoma, leukemia, carcinomas, melanoma).
Approximately 20% of patients will progress to ESRD in 20-30 years.
□ Laboratory Findings
Marked proteinuria. Nephrotic syndrome is found in many patients.
Microscopic hematuria may be present.
Autoantibodies against phospholipase A2 receptor (PLA2R-Ab), mostly of the IgG4 class, can be found in 70% of patients with primary membranous GN, and levels correlate with the clinical course and proteinuria.
Definitive diagnosis is by renal biopsy showing diagnostic findings by light, immunofluorescence, and electron microscopy.
GLOMERULONEPHRITIS, POSTINFECTIOUS
□ Definition
PIGN occurs after infection, usually with a nephritogenic strain of group A β-hemolytic Streptococcus (poststreptococcal GN [PSGN]).
It is the most common glomerular disorder in children between 5 and 15 years.
Pathogenesis is thought to be related to deposits of immune complexes in the GBM causing glomerular damage. Only 1-2% of cases progress to chronic GN.
□ Laboratory Findings
Evidence of infection with group A β-hemolytic Streptococcus by throat culture.
Serologic findings: antistreptolysin O (ASO) is the most commonly used laboratory test to confirm recent streptococcal infection. ASO titers remain elevated for several months in 50-80% of patients. Anti-DNase B is another serologic test to confirm a previous group A streptococcal infection.
Urinalysis
▼ Hematuria: gross or microscopic. Microscopic hematuria may occur during the initial febrile upper respiratory infection and then reappear with nephritis in 1-2 weeks and lasts for 2-12 months.
▼ RBC casts and dysmorphic RBCs show glomerular origin of hematuria.
▼ WBC casts and WBCs show inflammatory nature of the lesion.
▼ Granular and epithelial cell casts are present.
▼ Fatty casts and lipid droplets occur several weeks later and are not related to hyperlipidemia.
▼ Oliguria is frequent.
Random urinary protein/creatinine ratio is usually between 0.2 and 2 but may occasionally be in the nephrotic range.
Phenolsulfonphthalein (PSP) excretion is normal in cases of mild to moderate severity and increases with progression of disease. Azotemia with high urine specific gravity and normal PSP excretion usually indicates acute GN.
Blood Findings
▼ Azotemia is found in approximately 50% of patients.
▼ Leukocytosis and increased ESR.
▼ There is mild anemia, especially when edema is present. Anemia may be caused by hemodilution, bone marrow depression, or increased destruction of RBCs.
▼ Serum proteins are normal, or there are nonspecific decrease in albumin and increase in alpha-2 and sometimes beta and gamma regions.
▼ Serum C3 and total hemolytic complement activity (CH50) fall during the active disease and return to normal within 6-8 weeks in 80% of cases. If C3 is low for more than 8 weeks, lupus nephritis (LN) or MPGN should be considered.
▼ Serum cholesterol may be increased.
Renal biopsy shows characteristic findings with EM and immunofluorescence microscopy.
Chronic renal insufficiency is reported in ≤20% of patients.
GLOMERULONEPHRITIS, RAPIDLY PROGRESSIVE (CRESCENTIC)
□ Definition
RPGN is characterized by progressive loss of renal function and severe oliguria and renal failure that develop over a period of few weeks.
The histopathologic term “crescentic” refers to crescent formation, a nonspecific response to severe injury to the glomerular capillary wall. Patients may have RPGN in association with anti-glomerular membrane (anti-GBM) antibody disease (Goodpasture syndrome), a condition in which circulating antibodies are directed against an antigen in the GBM, resulting in progressive GN and, in approximately 60% of patients, pulmonary hemorrhage. RPGN can also be associated with Wegener granulomatosis, small vessel vasculitis, SLE, or cryoglobulinemia. Depending on the specific disorder, antineutrophil cytoplasmic antibodies (ANCA) can be present in the serum of RPGN patients.
□ Who Should Be Suspected?
Candidates include patients with rapidly developing oliguria or anuria and acute onset of hematuria and edema, especially in the presence of an underlying immunologically mediated systemic illness or following an infection or administration of certain drugs (e.g., allopurinol, hydralazine, rifampin, D-penicillamine).
Three types of RPGN can be distinguished according to the underlying mechanism of the glomerular injury:
▼ Type II: mediated by immune complexes (45% of cases; <5% of patients are ANCA positive).
□ Laboratory Findings
Laboratory workup is urgent to initiate therapy since untreated patients progress rapidly to ESRD. Renal biopsy findings establish the diagnosis and prognosis.
HEPATORENAL SYNDROME
□ Definition
Progressive renal failure that develops in patients with decompensated liver cirrhosis or fulminant hepatic failure.
This is classified as
▼ Type I: serum creatinine increases to >2.5 mg/dL within 2 weeks
▼ Type II: less severe and associated with gradual increase in serum creatinine (1.5-2.5 mg/dL) over few weeks or months
□ Who Should Be Suspected?
Patients with liver cirrhosis and ascites, especially following fluid loss (e.g., GI hemorrhage, diarrhea, or forced diuresis) or an intercurrent infection
Patients with other liver conditions that are associated with portal hypertension such as severe alcoholic hepatitis
□ Laboratory Findings
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
