C. Robert Cooke

Chronic hyponatremia due to resetting of the osmostat in a patient with gastric carcinoma

A 54-year-old schizophrenic patient who presented with hyponatremia and nephrotic-range proteinuria was subsequently discovered to have a gastric adenocarcinoma. Psychogenic water drinking, sodium depletion, and cardiac, adrenal, hepatic, and thyroid disease were excluded as causes of hyponatremia. The serum creatinine concentration was normal, and, although renal biopsy showed changes consistent with immune complex glomerulopathy, proteinuria remitted without treatment. Moderately severe hyponatremia persisted, and the diagnosis of gastric adenocarcinoma was made after the onset of early satiety 1 year later. Surgical exploration at the time of partial gastric resection revealed local metastatic lymph node involvement. Following the patients uneventful recovery from surgery, studies of osmoregulation of vasopressin release and renal water handling were performed to determine the cause of chronic hyponatremia refractory to sodium chloride administration. Oral water loading studies revealed normal urinary diluting ability and appropriate suppression of plasma vasopressin concentrations. However, hypertonic sodium chloride infusion studies revealed a highly significant correlation between plasma osmolality and plasma vasopressin concentration, and a low osmotic threshold for vasopressin release based on linear regression analysis of the plasma vasopressin response to increasing plasma osmolality. Low osmotic threshold for vasopressin release was confirmed by exponential (log linear) and parabolic methods of data analysis. The findings in these studies are consistent with the typical features of the reset osmostat variant of the syndrome of inappropriate antidiuresis. To our knowledge, this is the first report of the occurrence of this syndrome in association with gastric adenocarcinoma.

Pathological calcification of the lungs following intravenous administration of calcium.

Abstract A case is reported of extensive pulmonary calcification which occurred following the administration of large amounts of calcium gluconate, vitamin D and dihydrotachysterol in an effort to control severe manifestations of tetany. Whether or not the extreme refractoriness of the patients symptoms to the administration of calcium was due to other factors (i.e., hypomagnesemia) is not known. Pathological calcification of the lungs occurred to a degree disproportionate to any which may have escaped detection in other organs. There is no evidence that the lungs were altered in any way by factors which would account for this specific localization.

Acute Fulminant Lactic Acidosis Complicating Metastatic Cholangiocarcinoma

A patient with cholangiocarcinoma, metastatic to the liver and lungs, developed acute fulminant lactic acidosis in the absence of overt hepatic failure, sepsis, hypoxia, or circulatory failure. Despite extensive tumor replacement of hepatic parenchyma, no acid-base disorder was present during initial evaluation. The onset of acute lactic acidosis was temporally associated with the development of otherwise asymptomatic episodes of intermittent atrial arrhythmias. Once established, lactic acidosis was inexorably progressive, despite resolution of arrhythmias. Extensive areas of acute necrosis within the large hepatic metastases were demonstrated on postmortem examination, suggesting that local tissue ischemia, precipitated by cardiac arrhythmias, lead to excessive lactic acid production.

Case Report: Reversible Nephrotic Range Proteinuria and Renal Failure in Atheroembolic Renal Disease

A case is described in which atheroembolic renal disease was associated with nephrotic range proteinuria, sub-acute renal failure, severe hypertension and microhematuria, in the absence of typical peripheral stigmata of atheroemboli. Nephrotic range proteinuria has not been previously reported in atheroembolic renal disease. With sustained aggressive treatment of hypertension there was diminution and eventual clearing of the proteinuria accompanied by marked improvement in renal function. The histopathology, the indications for renal biopsy, and possible causes of proteinuria are discussed.

Favorable Outcome After Aggressive Treatment of Infection in a Diabetic Patient With MRSA-Related IgA Nephropathy

IgA immune complex deposition is not commonly seen with acute postinfectious glomerulonephritis secondary to staphylococcal infections. Its deposition is usually indicative of IgA nephropathy or Henoch-Schonlein purpura nephritis. We describe a patient with a history of diabetes mellitus who was admitted with methicillin resistant Staphylococcus aureus bacteremia and subsequent demonstration on renal biopsy of crescentic glomerulonephritis associated with codominant IgA and C3 immune deposits and early changes of diabetic nephropathy. After aggressive treatment of infection, which included bilateral metatarsal amputation and subsequent left below-the-knee amputation as well as antibiotic administration for persistent osteomyelitis, the patients renal function progressively improved with a reduction in serum creatinine concentration from 6.1 mg/dL (539 micromol/L) to 2.7 mg/dL (239 micromol/L). On a 3-year follow-up evaluation, his serum creatinine concentration was 1.7 mg/dL (150 micromol/L) and urine was negative for protein and blood.

Chloride-Resistant Metabolic Alkalosis in an Adult with Congenital Chloride Diarrhea

Congenital chloride diarrhea is a rare autosomal recessive disorder characterized by defective chloride-bicarbonate exchange in the ileum and possibly the colon, which results in diarrhea with marked losses of chloride in the stool [l-3]. Diarrhea usually begins within the first 24 hours after birth and may result in hypovolemia and chronic metabolic alkalosis due to chloride depletion. With aggressive sodium and potassium chloride replacement beginning in infancy, normal development and survival into adulthood are possible [2]. To our knowledge, this is the first report of a patient with this disorder who has survived to adulthood without major complications, except impairment of renal function, while receiving no specific therapy to correct the associated metabolic abnormalities. Chloride-responsive metabolic alkalosis related to chloride depletion and chloride-resistant metabolic alkalosis related to coexisting profound potassium depletion have both been observed in the course of clinical evaluation.

Osteomalacia and Secondary Hyperparathyroidism after Kidney Transplantation: Relationship to Vitamin D Deficiency

Secondary hyperparathyroidism is highly prevalent in patients with end-stage renal disease. After successful kidney transplantation, however, parathyroid glands gradually involute to normal size with subsequent normalization of intact parathyroid hormone (PTH), serum calcium, and phosphorous concentrations. This report describes a 48-year-old diabetic end-stage renal disease patient who underwent a successful cadaveric kidney transplant. Serum calcium and phosphorous concentrations normalized within 6 months. Three years later, he presented with complaints of proximal muscle weakness that was progressively worsening. Physical examination revealed temporal wasting and proximal muscle weakness. Detailed neurologic examination was unremarkable except for decreased vibratory sensation in both feet. Laboratory data showed stable allograft function (serum creatinine, 1.3 mg/dL), hypocalcemia, and hypophosphatemia with markedly elevated alkaline phosphatase level (726 IU/L) and intact PTH level (947 pg/mL). Further laboratory evaluation revealed poor nutritional status and severe deficiency of 25(OH)D (4.0 ng/mL). Past medical history included remote episodes of acute pancreatitis due to prior alcohol abuse. Computed tomography of the abdomen showed calcific atrophic pancreas, and steatorrhea was confirmed on stool studies. Decreased bone mineral density was noted by computed tomography bone density scan. Secondary hyperparathyroidism and osteomalacia had developed due to severe vitamin D deficiency, occurring as a result of previously unrecognized, minimally symptomatic pancreatic exocrine insufficiency. Treatment with vitamin D, calcium, and pancreatic enzyme replacement led to remarkable resolution of clinical symptoms and secondary hyperparathyroidism (intact PTH, 65 pg/mL after therapy) and resulted in significant improvement in bone mineralization. Factors associated with vitamin D deficiency in the chronic kidney disease and post-transplant patient population are reviewed.

Reversible Renal Failure Due to IgA Nephropathy Associated With Osteomyelitis

Clinical features of acute glomerulonephritis, with microscopic hematuria, red blood cell (RBC) casts, proteinuria, and acute renal insufficiency developed in a patient with chronic osteomyelitis. Before the development of osteomyelitis, renal function and findings on urinalysis were normal. Complete eradication of osteomyelitis by surgical amputation led to resolution of the abnormal urinary findings, and renal function returned to near pre-osteomyelitis levels. Although acute glomerular disease has been reported to occur as a rare complication of osteomyelitis, the unique feature of the present case was the histological finding of IgA nephropathy. There was no arthritis, purpura, skin rash, or gastrointestinal involvement to suggest a diagnosis of Henoch-Schönlein purpura and there was no evidence of chronic liver disease. The temporal relationship between the onset of the renal disease, which followed the development of chronic osteomyelitis, and its resolution following removal of the focus of infection, suggests that the IgA nephropathy may have been related directly to the osteomyelitis (secondary IgA nephropathy). Glomerular diseases associated with chronic bacterial infections, including osteomyelitis, are discussed, with emphasis on infections that have been associated with the development or exacerbation of IgA nephropathy.

Reversible changes in osmoregulation of vasopressin release due to impaired water excretion

Studies of renal water handling and the effects of altered hydration and posture on the osmoregulation of vasopressin release were performed on a chronically hyponatremic patient with complete cervical spinal cord transection at the C-5 level. Acute oral water loading studies showed marked reduction in free water clearance and urine diluting ability, despite appropriate suppression of plasma vasopressin concentrations. Orthostatic reductions in arterial blood pressure during head-up tilting and following the assumption of sitting posture were also demonstrable, and may have contributed to, but could not fully account for, the defect in renal water excretion, which persisted in supine posture. Hypertonic sodium chloride infusion studies performed before fluid restriction showed that low preinfusion plasma osmolality was associated with a reduced osmotic threshold for vasopressin release, which was subsequently corrected by a period of fluid restriction that restored the patients plasma osmolality to a normal level. This shift in osmotic threshold can be inferred from both linear regression and log-linear regression analysis of the data. These studies show that marked impairment of renal water excretion coupled with unrestricted water intake can result in altered osmoregulation of vasopressin release in association with persistent plasma hypo-osmolality, which can be corrected by fluid restriction.