7:00 PM, Sunday, March 23
Cotillion Ballroom South
Congenital and Hereditary Diseases of the Kidney: New Perspectives
Vivette D. D'Agati
Columbia University, College of Physicians and Surgeons
New York, New York
Click on each slide thumbnail image for an enlarged view
Robert B. Colvin
Massachusetts General Hospital
33 year old man presents with mild proteinuria (0.9 gm/d) and normal creatinine (0.8 gm/d). Since
adolescence had paresthesias of hands and feet, most severe when febrile. He also has longstanding
purple papules on flanks and groin area. No family history of renal disease. A renal biopsy (Biopsy A)
was performed and he was entered into a clinical trial. At the end of the trial, 11 months later a
second biopsy was performed (Biopsy B). Both biopsies were processed in epon for one micron sections and
EM. What was the disease and treatment and how did the pathology change?
This AGA male infant (XY karyotype) was delivered at 36 weeks to a 31-year-old G3P3 mother who received
no prenatal care. The placenta was large and the infant had widely spaced cranial sutures, large
anterior and posterior fontanelles, mild periorbital and moderate peripheral edema. He developed
respiratory distress and an infectious etiology was excluded. Evaluation revealed low serum albumin
(<1.0 g/dl) and protein (2.6 g/dl) with nephrotic-range proteinuria; BUN and Cr were 12 mg/dl and 0.2
mg/dl, respectively. Renal sonogram showed enlarged kidneys with diffuse bilateral echogenicity. An
open biopsy was performed. The infant failed to thrive and several bouts of sepsis followed. His
proteinuria was unresponsive to drug management but his renal function remained intact. A unilateral
nephrectomy was performed at 4 months of age; persistent heavy proteinuria prompted removal of
the second kidney at 7.5 months.
Johns Hopkins Hospital
A 4 year old African-American girl was admitted to the hospital with a one week history of vomiting,
anorexia, and lethargy. There was a history of polydipsia without reported polyuria or dysuria.
Physical exam was remarkable for height 93 cm (<5th percentile, height age 2.75 years), weight 11.5 kg
(<5th percentile), hypotonia, and evidence of dehydration. There was no edema. Blood pressure was
100/60. Family history was positive for hypertension, but otherwise negative for renal disease.
During the first week of hospitalization, laboratory work-up showed (normal range for age listed in
parentheses for abnormal values only): serum sodium 125-135 (138-145), potassium 1.8-2.8 (3.4-4.9),
chloride 82-92 (97-110), and bicarbonate 27-32 (21-28) mmol/L. BUN was 7 mg/dl and serum creatinine 0.4
mg/dl. Total serum calcium was 9.4 mg/dl and magnesium 2.1 mg/dl. Total serum protein was 7.3 g/dl and
albumin 4.4 g/dl. Urinalysis showed 3+ protein, with no glucose, RBC, or WBC. A 24 hour urine
collection showed specific gravity 1.010 (1.015-1.025), osmolality 224 mosmol/kg (300-900), protein 290
mg (50-80), protein/creatinine ratio 1.1 (<0.2), sodium 54 mmol, potassium 25 mmol, chloride 50 mmol
(15-40), calcium 71 mg. Renal ultrasound showed low-normal kidney sizes with increased echogenicity but
no apparent nephrocalcinosis. ANA, anti-double-stranded DNA, and Sjogren's SS-A and SS-B antibodies were
negative, and serum C3 and C4 were normal. Serum aldosterone was 167 ng/dl (normal <40), plasma renin
activity 1542 mU/ml (normal <100), and serum 6-keto-prostaglandin F1a (a product of renal prostaglandin
metabolism) 13 pg/ml (normal <10).
The clinical impression was probable Bartter's syndrome, although this did not explain the proteinuria.
Largely for this reason, an open renal biopsy was performed.
M. Barry Stokes
New York University Medical Center
New York, New York
A 28-year old American-born Chinese man presented with bilateral ankle edema, foamy urine, sore throat,
and new-onset of hypertension (blood pressure 164/114 mm Hg). Urinalysis showed 16 to 20 RBCs/HPF and 24
hour urine collection protein contained 3.9 g protein. Laboratory investigations revealed blood urea
nitrogen 34 mg/dL, serum creatinine 2.6 mg/dL, serum albumin 2.5 g/dL, total serum protein 5.0 g/dL,
cholesterol 499 mg/dL, triglycerides 485 mg /dL, low-density lipoprotein (LDL) 275 mg/dL and glucose 112
mg/dL. Urine electrophoresis revealed predominantly albumin. Serologic tests for antinuclear antigen,
cryoglobulin, paraproteins, and hepatitis B surface antigen were all negative. Anti-streptolysin-O
titer, serum C3 and serum C4 levels were within normal limits. Renal ultrasound revealed normal sized
kidneys with diffusely increased echogenicity of the renal parenchyma. The patient had no significant
past medical history and neither his parents nor his two sisters had a known history of renal disease. A
renal biopsy was performed.
Vanderbilt University Medical Center
A three-year-old white boy presented to the emergency room department after he developed "tea-colored"
urine. He was given antibiotics (not specified) in the emergency department and referred to his primary
physician. There was no periorbital or extremity swelling, petechiae, purpura, rashes, joint swelling or
pain. He had upper respiratory symptoms with low-grade fever and a "croupy cough". The past medical
history was significant for a normal vaginal delivery induced four weeks before term secondary to
recurrent "UTI's" in the mother. The family history was significant for approximately 40 episodes of
"UTI's" not further characterized in the mother, as well as a history of one episode of nephrolithiasis
in the mother. The father also had a history of UTI's and mild vesicoureteral reflux as a child. The
father had a history of persistent microscopic hematuria with onset in childhood, and many episodes of
gross hematuria between the ages of five and seven years. He had been followed by a pediatric
nephrologist. The father currently at age 36 still had positive dipstick for blood with occasional RBCs,
no RBC casts. He had normal renal function (Screat 0.9) and no proteinuria, blood pressure 100/64 mm Hg
on no meds. The father's mother at some point had "kidney trouble" but no details were known. Both the
father's parents were alive and well.
On examination, the child was afebrile, with blood pressure 86/59 mm Hg. He weighed 13 kg (25%), and was
93 cm tall (25%). He appeared alert and playful and was in no apparent distress. The physical exam was
unremarkable, and further review of system was noncontributory. Laboratory examination showed WBC
7000/mm3, PCV 36%, platelets 316,000 mm3. The differential showed 31% neutrophils, 54% lymphocytes and
6% atypical lymphocytes. Electrolytes were normal, BUN was 9 mg/dl, serum creatinine 0.3 mg/dl, Ca 2+
8.8 mg/dl, phosphorus 4.5 mg/dl, glucose 69 mg/dl, albumin 3.3 g/dl, total biliubin 0.5 mg/dl, alkaline
phosphatase 154 U/L, SGOT 55 U/l. An ASO titer was <58 (<125 is neg), and streptozyme was <1:100. C3
was slightly decreased at 84 units mg/dl (88-201 normal), C4 was 38 mg/dl (15/45), IgA level was 52 mg/dl
(25-154 mg/dl normal), and ANA and ANCA tests were negative. Urinalysis showed a specific gravity of
1.020, pH 7, 2+ protein and large blood positivity, with negative leukocyte esterase and nitrogen tests.
The microscopic exam showed 5 to 10 WBCs and numerous dysmorphic RBCs and occasional RBC casts. Renal
ultrasound showed normal kidneys with normal shape and size (7 cm), without cysts, stones or masses. The
urine protein/creatinine ratio was 0.4.
The patient was followed up in the Pediatric Renal Clinic with close monitoring of renal function and
hematuria. The hematuria persisted over the next six months, and diagnostic procedures were performed.