Sunday, November 21, 2004

Five Month-Old With Renal Failure and Hematuria

Clinical History: A five month-old female with no previously established congenital abnormalities presents with hematuria and severe acute renal failure. A renal biopsy was performed and demonstrated severe tubular damage with extensive crystal deposition associated with active tubulointerstitial nephritis (TIN) and acute tubular necrosis (ATN). The glomeruli displayed immature features appropriate for the patient’s age with insignificant obsolscence (<5%).

H&E stain, 100X

H&E stain and polarized light, 50X

Transmission electron microscopy image

Renal Biopsy Diagnosis: Primary Hyperoxaluria

Oxalosis occurs when the kidneys do not eliminate sufficient calcium oxalate crystals from the body through the urine. Because the kidneys stop functioning, oxalate crystals are deposited elsewhere in the body such as the eyes and other major organs.

Primary hyperoxaluria is a rare condition that is usually caused by a defective gene in liver and other cells. There are three types of primary hyperoxaluria: I, II and III. Types I and II are both autosomal recessive disorders caused by liver and other cell enzyme deficiencies but type II is milder and does not usually cause end-stage renal disease. Type III is poorly defined with an unknown cause. Type I primary hyperoxaluria is estimated to occur in 1 per 60,000 to 120,000 live births; it is more common in some Mediterranean countries, such as Tunisia. The incidence of type II primary hyperoxaluria is unknown; it is less common than type 1.

Primary hyperoxaluria is characterized by the overproduction of a substance called oxalate (or oxalic acid). In the kidneys, the excess oxalate combines with calcium to form calcium oxalate, a hard compound that is the main component of kidney stones. Deposits of calcium oxalate can lead to kidney damage, kidney failure, and injury to other organs. Sugar and amino acid metabolism produces glyoxylate that is normally converted to the amino acid glycine or to a compound called glycolate through the action of alanine-glyoxylate aminotransferase (AGXT gene) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR gene), respectively. Mutations in the AGXT (type I disease) or GRHPR (type II disease) gene cause a shortage of these enzymes, which prevents the conversion of glyoxylate to glycine or glycolate. As levels of glyoxylate build up, it is converted to oxalate instead. Oxalate combines with calcium to form calcium oxalate, which is what causes the severe kidney and other organ damage.

The diagnosis of hyperoxaluria is made by measuring the oxalic acid level in the urine of affected people and a specific diagnosis is obtained from enzyme analysis of a liver biopsy. A prenatal diagnosis may require fetal liver biopsy. It is difficult to predict the severity of hyperoxaluria that is related to supersaturation of urine oxalate and calcium. Combined liver and kidney transplantation is the current definitive therapy for patients with severe disease.

Online information:

1. van Woerden CS, Groothoff JW, et al: Clinical implications of mutation analysis in primary hyperoxaluria type 1. Kidney Int. 2004 Aug;66(2):746-52.
2. Rumsby G, Williams E, et al: Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperoxalurias. Kidney Int. 2004 Sep;66(3):959-63.
3. Danpure CJ, Rumsby G.: Molecular aetiology of primary hyperoxaluria and its implications for clinical management. Expert Rev Mol Med. 2004 Jan 9;2004:1-16.
4. Millan MT, Berquist WE, et al: One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria: a single-center experience. Transplantation. 2003 Nov 27;76(10):1458-63.

Unexplained Acute Renal Failure

Clinical history: This case involves a 53 year-old man who had previously been healthy but presented with relatively acute renal failure (serum creatinine of 13.0 mg/dl), unclassified myeloproliferative disease and proteinuria (2 grams per 24-hours).

Trichrome stain, 200X: atypical tubular casts

Trichrome stain, 400X: atypical tubular casts

Immunofluorescence analysis, 200X: kappa light chain

Renal Biopsy Diagnosis: Monoclonal Immunoglobulin Cast Nephropathy - Kappa Light Chain Type

Discussion: Path Logic has experienced an increase in the diagnosis of monoclonal immunoglobulin cast nephropathy presenting with unexplained acute renal failure (ARF) associated with undiagnosed or unclassified myeloproliferative disorder. The ARF is most likely due to a combination of dehydration, varying degrees of tubular necrosis (ATN) and the cast nephropathy. There is usually no evidence of amyloidosis in these cases. This trend is likely to continue with the aging population in the US. The early diagnosis of this disorder is creating treatment decision problems for both nephrologists and hematology/oncology consultants who are reluctant to treat undiagnosed or unclassified myeloproliferative disorders.

Mead GP, Carr-Smith HD, et al: Serum free light chains for monitoring multiple myeloma. Br J Haematol. 2004 Aug;126(3):348-54.
Markowitz GS.: Dysproteinemia and the kidney. Adv Anat Pathol. 2004 Jan;11(1):49-63.
Kyle RA, Gertz MA, et al: Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003 Jan;78(1):21-33.

Saturday, November 20, 2004

Recurrent Headaches

Case history:
This case involves a 38 year-old woman who apparently had complained to her local community healthcare clinic of recurrent headaches for over a year. She was reassured that these were “migraine headaches” and she was treated with over the counter medications and verbal support. Finally, she presented to the ER with persistent headache and vomiting. She was found to have severe hypertension (230/131) and renal failure.

Silver stain, 400X

Silver stain, 400X

Trichrome stain, 400X

Acute Thrombotic Microangiopathy Secondary To Malignant Hypertension

Thrombotic microangiopathy is a diagnosis that encompasses a group of disorders including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), antiphospholipid syndrome (APS), malignant hypertension and others. These disorders have in common microangiopathic hemolytic anemia, thrombocytopenia, and several variable signs of organ damage due to thrombosis or platelet aggregation involving the microcirculation.

1. Levine SR, Brey RL, et al: Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA. 2004 Feb 4;291(5):576-84.
2. Cervera R, Balasch J.: The management of pregnant patients with antiphospholipid syndrome. Lupus. 2004;13(9):683-7.
3. Obermoser G, Bitterlich W, et al: Clinical significance of anticardiolipin and anti-beta2-glycoprotein I antibodies. Int Arch Allergy Immunol. 2004 Oct;135(2):148-53. Epub 2004 Sep 02.
4. Blank M, Asherson RA, Cervera R, Shoenfeld Y.: Antiphospholipid syndrome infectious origin. J Clin Immunol. 2004 Jan;24(1):12-23.
5. Coppo P, Bussel A, et al: High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome. Medicine (Baltimore) 2003 Jan;82(1):27-38.
6. Moake JL. Thrombotic microangiopathies. N Engl J Med 2002 Aug 22;347(8):589-600.
7. Nzerue CM, Hewan-Lowe K, Pierangeli S, Harris EN.: "Black swan in the kidney": renal involvement in the antiphospholipid antibody syndrome. Kidney Int 2002 Sep;62(3):733-44.
8. Saikali JA, Truong LD, Suki WN.: Sirolimus may promote thrombotic microangiopathy. Am J Transplant 2003 Feb;3(2):229-30.
9. Lip GY, Beevers M, Beevers DG.: Does renal function improve after diagnosis of malignant phase hypertension? J Hypertens 1997 Nov; 15(11):1309-15.

Welcome to Nephropath!

Human kidney, bi-halved

Busy nephrologists can now enjoy viewing brief nephrology cases that focus on the diagnostic renal biopsy results. Short clinical histories are presented when available. No private patient or physician information is presented as Path Logic (the source pathology lab for this blog) does not wish to compromise anyone’s privacy or violate HIPPA compliance rules which are always strictly enforced. Comments are welcome.