Donald S. Fraley

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: PRESENTATION, COMPLICATIONS, AND PROGNOSIS

Fifty-three symptomatic adults with autosomal dominant polycystic kidney disease were studied retrospectively for a mean follow-up of 12 years (range 10 months to 33 years). Diagnosis was confirmed by either x-ray, ultrasound, laparotomy, or autopsy. Commonest presenting clinical findings were flank pain (30%), hypertension (21%), symptomatic urinary tract infection (UTI) (19%), gross hematuria (19%), and palpable masses (15%). A total of nine patients (17%) progressed to end-stage renal disease. Change in renal function measured using the reciprocal of plasma creatinine plotted against time was linear for each individual patient with a maximum functional decline of 0.7 mg/dL/yr (slope = -0.07). Past the age of sixty renal failure was uncommon. Easily controlled hypertension developed in 64% attended by mild retinopathy. UTIs were common (53%), often recurrent (61%), precipitated by instrumentation in 6 of 14 patients (43%), leading to death in two (33%). Renal calculi were extremely common (34%) and had no defined metabolic cause. The presence of hematuria (64%), gross or microscopic, bore no relationship to the decline in renal function. Pregnancy was normal in these patients with no increase in fetal or maternal morbidity or mortality. We conclude the following: Renal functional deterioration is linear, less than previously reported, and bears no relationship to hematuria. Hypertension is common, easily treated, and causes minor end-organ damage. Renal calculi are frequent. Urinary tract instrumentation often induces infection with considerable morbidity and mortality and must be avoided. Pregnancy is not contraindicated if renal function is normal. The prognosis for survival in this disease is better than previously reported.

Fenoprofen nephropathy: lipoid nephrosis and interstitial nephritis. A possible T-lymphocyte disorder.

Five patients are presented, each of whom had an acute idiosyncratic reaction to fenoprofen calcium (Nalfon) characterized by acute renal failure and marked proteinuria. Renal pathology was similar in all patients. Light microscopy revealed marked lymphocytic inflammatory infiltrates and normal glomeruli. Immunofluorescent staining was minimal or absent. Electron microscopy showed fusion of podocytes in otherwise normal glomeruli. Two patients were studied using T-cell and B-cell specific fluorescent staining, which revealed that the interstitial infiltrates were composed exclusively of T-lymphocytes. This finding is considered in relation to prior experimental and theoretic work. It is suggested that the various clinical and pathologic findings in fenoprofen nephropathy are all manifestations of a disordered cell-mediated immunity.

Stimulation of Lactate Production by Administration of Bicarbonate in a Patient with a Solid Neoplasm and Lactic Acidosis

LACTIC acidosis associated with acute leukemia has been attributed to overproduction of lactic acid by the tumor cells, 1 2 3 whereas lactic acidosis in solid, nonhematologic neoplasia with hepatic...

Sustained remission of membranous glomerulonephritis after cyclophosphamide and prednisone.

OBJECTIVE To determine the effect of cyclophosphamide and prednisone on progressive renal failure and on nephrotic features in patients with membranous glomerulonephritis. DESIGN Prospective, nonrandomized time series. SETTING Outpatient clinic at a university medical center. PATIENTS Eleven consecutive patients with biopsy-proven membranous glomerulonephritis and rising plasma creatinine levels over at least 6 months. INTERVENTION Cyclophosphamide and prednisone in ten patients and cyclophosphamide alone in one patient. MEASUREMENTS AND MAIN RESULTS In ten patients treated with both agents, the median plasma creatinine rose 53 mumol/L (0.6 mg/dL) over the months before treatment from 141 to 194 mumol/L (1.6 to 2.2 mg/dL) (95% CI, 27 to 141 mumol/L; P = 0.002). After combined therapy for 6 months, the median plasma creatinine fell to 133 mumol/L (1.5 mg/dL) for a median decline of 62 mumol/L (0.7 mg/dL) (CI, 44 to 150 mumol/L; P = 0.006). Pretreatment plasma creatinine levels, which ranged from 159 to 371 mumol/L (1.8 to 4.2 mg/dL), decreased in the ten patients by 6 months and remained stable in seven of the eight patients followed 24 to 54 months after therapy was completed. The median urine protein excretion decreased by 9.6 g/d with 12 months of therapy in the ten patients from 11.9 to 2.3 g/d (CI, 6.0 to 15.1 g/d; P less than 0.001). The median plasma albumin rose by 14 g/L from 24 to 38 g/L (CI, 11 to 19 g/L; P less than 0.001). The median plasma cholesterol fell by 3.26 mumol/L (140 mg/dL) from 10.45 to 6.52 mumol/L (405 to 252 mg/dL) (CI, 1.42 to 7.16 mumol/L; P = 0.01). One patient who had a relapse 30 months after completing therapy responded to re-treatment with renal function and nephrotic variables returning toward normal. The eleventh patient received cyclophosphamide alone and had a course similar to that of the combined therapy group. CONCLUSION Cyclophosphamide plus prednisone can promote prolonged remissions in membranous glomerulonephritis even when renal function is already declining.

An Extrarenal Role for Parathyroid Hormone in the Disposal of Acute Acid Loads in Rats and Dogs

Acid infusion studies were performed in nephrectomized rats and dogs with either intact parathyroid glands (intact) or after thyroparathyroidectomy (thyroparathyroidectomized [TPTX]) to determine the role of parathyroid hormone (PTH) in extrarenal disposal and buffering of acutely administered acid. 29 intact rats given 5 mM/kg HCl and 6 intact dogs given 7 mM/kg HCl developed severe metabolic acidosis but all survived. However, each of 12 TPTX rats and 4 TPTX dogs given the same acid loads died. Intact rats and dogs buffered 39 and 50% of administered acid extracellularly, respectively, whereas extracellular buffering of administered acid was 97 and 78% in TPTX rats and dogs, respectively. 17 TPTX rats and 6 TPTX dogs given synthetic PTH 2 h before acid infusion survived. The blood bicarbonate and extracellular buffering in these animals, measured 2 h after acid infusion, was similar to intact animals. Changes in liver, heart, and skeletal muscle pH determined from [(14)C]5,5-dimethyl-2,4 oxazolidinedione distribution seemed insufficient to account for the increased cell buffering of PTH-replaced animals. Indeed, muscle pH in TPTX dogs given PTH and acid was only 0.06 pH units lower than in control dogs given no acid, suggesting that another tissue, presumably bone, was the target for PTH-mediated increased cell buffering. This conclusion was supported by the observation that PTH did not alter the pH of intact rat diaphragms in vitro. These results indicate that PTH is necessary for the optimal buffering of large, acute acid loads presumably by increasing bone buffering.

Long-term follow-up of aggressively treated idiopathic rapidly progressive glomerulonephritis.

PURPOSE We wanted to examine the long-term effects of aggressively treating idiopathic rapidly progressive glomerulonephritis (RPGN), with a particular focus on clinically characterizing the patient population, assessing the short- and long-term effects of therapy on renal function, and determining complications of the therapy. PATIENTS AND METHODS Twenty-three consecutive patients with RPGN were treated and followed from one to 11 years. On renal biopsy, 13 had immune complexes, eight had no immune complexes, and two had antiglomerular basement membrane deposits. All had greater than 25 percent crescents and 19 of 23 had greater than 50 percent crescents. Every patient responded on a short-term basis to either large-dose pulse methylprednisolone or plasma exchange, with reduction of the mean plasma creatinine level from 6.5 +/- 2.0 mg/dl to 2.9 +/- 1.0 mg/dl (p less than 0.001). Each patient received oral prednisone and all but one received cyclophosphamide. RESULTS Three died of non-renal causes. Fifty percent of the remaining 20 patients maintained stable renal function for at least two years. Four of nine patients followed-up for longer than two years had a relapse, but all responded again to therapy. No characteristic clinical symptoms predicting relapse were found, although nearly all had hematuria and proteinuria. Complications of therapy were frequent and may have contributed to death in two patients. CONCLUSION Thus, long remissions are seen in most patients with RPGN treated aggressively.

The Use of Streptokinase to Treat Renal Artery Thromboembolism

The effects of streptokinase are difficult to determine. Furthermore, it has toxic side effects, and renal function may not recover from its use. However, because of favorable experiences with this drug in the early treatment of venous thromboembolism and following myocardial infarction, as well as the favorable findings with early perfusion in the dog model, the use of local streptokinase may be justified if the infusion is begun early, preferably within four to six hours.

Rupture of Ovarian Cyst: Massive Hemoperitoneum in Continuous Ambulatory Peritoneal Dialysis Patients: Diagnosis and Treatment

Two women on continuous ambulatory peritoneal dialysis (CAPD) developed recurrent episodes of hemoperitoneum while in the reproductive age group. Initially, both were thought to have mechanical problems with the peritoneal catheter system. A laparotomy was performed in the first patient, and a bleeding ovarian cyst was identified. The second patient had ovarian cysts documented by ultrasound. Thus, abdominal pain and bloody dialysate should not just be ascribed to catheter-related problems. The second patients midcycle bleeding was suppressed with birth control pills.

Plasmapheresis as Sole Therapy in a Patient With Essential Mixed Cryoglobulinemia

An 82-year-old woman with essential mixed cryoglobulinemia type II (IgM K IgG) presented with moderate renal failure and nephritic syndrome. Mesangiocapillary glomerulonephritis with mesangial and subendothelial granular deposits containing IgG, IgM, and C3 in conjunction with small-vessel vasculitis was seen on renal biopsy. Renal symptomatology preceded by a period of 10 months the development of leg ulcers and purpura. The onset of the skin lesions was accompanied by an acute decline of renal function and an increase in liver alkaline phosphatase. Plasmapheresis with a 50% plasma exchange each week over 12 weeks led to improvement in renal function, healing of leg ulcerations, disappearance of purpura, and a return to the baseline of alkaline phosphatase in association with the disappearance of circulating cryoglobulins.

Genital Edema in Patients on Continuous Ambulatory Peritoneal Dialysis

Severe genital edema is a well-described complication of continuous ambulatory peritoneal dialysis (CAPD). Leakage of dialysate fluid from defects in the peritoneum may occur from clinically detectable and undetectable inguinal hernias, defects at the catheter insertion site, or other defects in the peritoneal membrane. We describe 3 patients (who underwent five surgical procedures), illustrating the complexity of the problem. In 2 patients, unsuccessful surgical repairs (1 catheter replacement, 1 hernia repair) were performed based on misleading radiologic findings using intraperitoneal contrast without computerized tomography (CT) scanning. The use of CT scanning with intraperitoneal contrast led to the correct diagnosis and prompt surgical correction in both patients so studied. One patient had leakage from a clinically undetectable inguinal hernia, and the other had a peritoneal defect at the Tenckhoff insertion site which was only demonstrated following a period of upright posture with a 3-liter exchange. Our experience and a review of the literature convinces us that a CT scan of the abdomen utilizing radiocontrast material added to the dialysate accurately identifies the site of leakage in CAPD patients who develop genital edema. Thus, the CT scan can help avoid unnecessary surgery and prolonged hospitalization in CAPD patients who develop genital edema.