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Nephrology Kidney Manifestations of Deposition Diseases Various kidney diseases are associated with deposition of immunoglobulin (lg) and non-lg proteins. Monoclonal Ig deposits are most commonly caused by: . myeloma . WaldenstrOm macroglobulinemia . chronic lymphocytic leukemia Disease may also be caused by clonal expansion of Ig secreting cells that do not meet the strict definition of these disorders but may cause kidney disease, which has been termed monoclonal gammopathy of renal significance. The most common pathologic findings associated with monoclonal Ig deposition include proliferative glomerulonephritis, AL amyloidosis, and type 1 cryoglobulinemia. Polyclonal Ig deposits are associated with mixed cryoglobulinemias. Kidney manifestations of monoclonal gammopathies may include proteinuria (sometimes nephrotic range), tubular dysfunc tion, hypertension, and kidney failure. Management is focused on treatment olthe underlying monoclonal disorder.

The most common pathologic findings associated with monoclonal Ig deposition include proliferative glomerulonephritis, AL amyloidosis, and type 1 cryoglobulinemia. Polyclonal Ig deposits are associated with mixed cryoglobulinemias. Kidney manifestations of monoclonal gammopathies may include proteinuria (sometimes nephrotic range), tubular dysfunc tion, hypertension, and kidney failure. Management is focused on treatment olthe underlying monoclonal disorder. STUDY TABLE: Seleaed Deposition Diseases Condition Pathology Clinical Syndrome Amyloidosis Deposits that stain apple green with Congo Proteinuria or nephrotic syndrome red Monoclonal immunoglobulin Congo red-negative light or heavy chain Proteinuria or nephrotic syndrome deposition disease deposits Multiple myeloma Serum free light chains are extremely Acute kidney injury elevated (usually >50 mg/dL) Acute or CKD associated with Fanconi Accumulation of light chains in the renal syndrome tubule (cast nephropathy) Light chains absorb and crystallize in proximal tubular cells Cryoglobulinemia Vasculitic syndrome with GN with Most often associated with type ll mem branoproliferative featu res cryoglobulins (HCV infeaion) Nephritic syndrome, RPGN Low C4 (sometimes C3) Monoclonal gammopathy of renal Most often caused by monoclonal antibody The presence of MGUS with kidney significance deposition in the k idney abnormalities, including proteinuria, nephrotic syndrome, Fanconi syndrome, GN

STUDY TABLE: Seleaed Deposition Diseases Condition Pathology Clinical Syndrome Amyloidosis Deposits that stain apple green with Congo Proteinuria or nephrotic syndrome red Monoclonal immunoglobulin Congo red-negative light or heavy chain Proteinuria or nephrotic syndrome deposition disease deposits Multiple myeloma Serum free light chains are extremely Acute kidney injury elevated (usually >50 mg/dL) Acute or CKD associated with Fanconi Accumulation of light chains in the renal syndrome tubule (cast nephropathy) Light chains absorb and crystallize in proximal tubular cells Cryoglobulinemia Vasculitic syndrome with GN with Most often associated with type ll mem branoproliferative featu res cryoglobulins (HCV infeaion) Nephritic syndrome, RPGN Low C4 (sometimes C3) Monoclonal gammopathy of renal Most often caused by monoclonal antibody The presence of MGUS with kidney significance deposition in the k idney abnormalities, including proteinuria, nephrotic syndrome, Fanconi syndrome, GN Autosomal Dominant Polycystic Kidney Disease Diagnosis The hallmark of ADPKD is large kidneys with multiple kidney cysts resulting from genetic mutations in pI(D1 and pI(D2. More than 90'1, of PKD is as an autosomal dominant trait.

Autosomal Dominant Polycystic Kidney Disease Diagnosis The hallmark of ADPKD is large kidneys with multiple kidney cysts resulting from genetic mutations in pI(D1 and pI(D2. More than 90'1, of PKD is as an autosomal dominant trait. Kidney ultrasonography is used to diagnose ADPKD. In patients with a family history of ADpKD, the number of cysts needed for diagnosis increases with age. 278

Nephrology DOT{'T BE TRICKED . Direct mutational analysis of the PKDI and PI(D2 genes is reserved for equivocal cases following imaging. Hypertension is a common presentation. More than 50% of patients develop recurrent flank or back pain from kidney stones, cyst rupture or hemorrhage, or infection. A ruptured intracranial cerebral aneurysm is the most serious extrarenal complication of ADPKD and occurs most commonly in patients with a family history of hemorrhagic stroke or intracranial cerebral aneurysm. Treatment ADPKD has no specific treatments . Treat hypertension with an ACE inhibitor or an ARB. . Treat cyst infection or pyelonephritis with fluoroquinolones or trimethoprim-sulfamethoxazole. . Tolvaptan has been approved to reduce the rate of increase in kidney size and loss of GFR, but poor tolerance, hepatotox- icity, and expense limit its use. Patients with a history of ADPKD, particularly those with a family history of intracranial aneurysm, should be offered screening for aneurysm by CTA or MRA. DON'T BE TRICKED . Up to 25'2, of patients with newly diagnosed ADPKD may have a negative family history owing to mild disease in an affected parent, spontaneous germline mutation, or earlier death from other causes. lnherited Collagen Type lV-Related Nephropathies Two relevant inherited collagen type IV-related nephropathies: . hereditary nephritis . thin GBM disease Hereditary nephritis (Alport syndrome) is a glomerular disease associated with sensorineural hearing loss and characteristic ocular flndings such as lenticonus. Proteinuria, hypertension, and CKD usually develop over time. End stage kidney disease occurs between the late teenage years and the fourth decade of lif'e. Management is supportive, including blood pressure control with RAS blockade. Thin GBM disease (benign familial hematuria) manifests as microscopic or macroscopic hematuria without significant pro teinuria and a family history olsimilar phenotype, usually first appearing in childhood. Long-term prognosis is excellent.

. hereditary nephritis . thin GBM disease Hereditary nephritis (Alport syndrome) is a glomerular disease associated with sensorineural hearing loss and characteristic ocular flndings such as lenticonus. Proteinuria, hypertension, and CKD usually develop over time. End stage kidney disease occurs between the late teenage years and the fourth decade of lif'e. Management is supportive, including blood pressure control with RAS blockade. Thin GBM disease (benign familial hematuria) manifests as microscopic or macroscopic hematuria without significant pro teinuria and a family history olsimilar phenotype, usually first appearing in childhood. Long-term prognosis is excellent. Acute Kidney lnjury Diagnosis and Testing AKI is defined as an abrupt elevation in the serum creatinine concentration or a decrease in urine output. The cause may be secondary to prerenal causes, intrinsic kidney disease, or postrenal obstruction of urine outflow. Prerenal and postrenal causes must be distinguished from intrinsic renal parenchymal disease because they are often rapidly reversible. AKI is also divided into oliguric (<4OO mLl24 h) and nonoliguric (>400 mLl24h) forms. The lower the urine output, the worse the prognosis. 279