Melvin E. Laski

Outcomes research in dialysis.

Worldwide, the number of patients with end stage renal disease (ESRD) and the number of ESRD patients receiving renal replacement therapy is growing. In the United States the number of patients enrolled in the Medicare-funded ESRD program has grown substantially, from approximately 10000 beneficiaries in 1973 to 340261 as of December 31, 1999. United States has the highest incidence ESRD of 317 per million population. Despite the magnitude of resources committed to the treatment of ESRD and the substantial improvements in the quality of dialysis therapy, these patients continue to experience significant mortality and morbidity, and reduced quality of life. Moreover, 50% of dialysis patients have 3 or more comorbid conditions, the mean number of hospital days per year is approximately 14 per patient, and self reported quality of life is far lower in dialysis patients than in general population. The most desirable interventions are those that specifically target measurable global outcomes such as mortality, morbidity, and health care costs. Nevertheless, patient outcomes that have shown links with these global outcomes may also be appropriate targets for intervention. This article will briefly review the available literature to discuss the role of important clinical indicators on dialysis outcomes and their impact on continuing care of ESRD population.

Acid-base disorders in medicine

The practice of internal medicine involves daily exposure to abnormalities of acid-base balance. A wide variety of disease states either predispose patients to develop these conditions or lead to the use of medications that alter renal, gastrointestinal, or pulmonary function and secondarily alter acid-base balance. In addition, primary acid-base disease follows specific forms of renal tubular dysfunction (renal tubular acidosis). We review the acid-base physiologic functions of the kidney and gastrointestinal tract and the current understanding of acid-base pathophysiologic conditions. This includes a review of whole animal and renal tubular physiologic characteristics and a discussion of the current knowledge of the molecular biology of acid-base transport. We stress an approach to diagnosis that relies on knowledge of acid-base physiologic function, and we include discussion of the appropriate treatment of each disorder considered. Finally, we include a discussion of the effects of acidosis and alkalosis on human physiologic functions.

Sirolimus induced granulomatous interstitial pneumonitis

Objectives Report a case of sirolimus induced granulomatous pneumonitis. Background Sirolimus is used in clinical transplantation as an immunosuppressive agent. Pulmonary toxicity does occur, but only a few cases of sirolimus associated granulomatous interstitial pneumonitis have been reported. Methods Case report and literature review. Results This 53-year-old woman with ESRD from polycystic kidney disease status post deceased donor kidney transplantation presented with fever, progressive dyspnea, and hypoxia for two weeks. She had been switched to sirolimus two months before admission. A CT scan of the chest revealed bilateral ill-defined patchy ground glass opacities. Extensive investigations were negative for infection. Video-assisted thoracoscopic biopsy showed granulomatous interstitial pneumonitis. Her symptoms and infiltrates resolved after sirolimus discontinuation and corticosteroid treatment. Conclusions Drugs induced pneumonitis should always be considered in transplant patients after infectious or other etiologies have been excluded. Sirolimus can cause granulomatous infiltrates in the lung possibly secondary to T-cell mediated hypersensitivity.

Diseases of Renal Adenosine Triphosphatase

Most renal transport is a primary or secondary result of the action of one of three membrane bound ion translocating ATPase pumps. The proximal tubule mechanisms for the reabsorption of salt, volume, organic compounds, phosphate, and most bicarbonate reabsorption depend upon the generation and maintenance of a low intracellular sodium concentration by the basolateral membrane Na-K-ATPase pump. The reabsorption of fluid and salt in the loop of Henle is similarly dependent on the energy provided by Na-K-ATPase activity. Some proximal tubule bicarbonate reabsorption and all distal nephron proton excretion is a product of one of two proton translocating ATPase pumps, either an electrogenie H-ATPase or an electroneutral H-K-ATPase. In this article, the authors review the biochemistry and physiology of pump activity and consider the pathophysiology of proximal and distal renal tubular acidosis, the Fanconi syndrome, and Bartters syndrome as disorders of ATPase pump function.

Antineutrophil Cytoplasmic Antibodies-Negative Pauci-Immune Crescentic Glomerulonephritis Associated with Multiple Myeloma.

Pauci-immune crescentic glomerulonephritis (PICGN) is most commonly associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of chronic, sclerosing ANCA-negative PICGN discovered when a patient presented with multiple myeloma. A 57-year-old woman presented with complaints of nausea, emesis and weakness. She was found to be in renal failure with a serum creatinine of 9.4 mg/dl, mild hyperkalemia and acidosis. She was noted to have normochromic, normocytic anemia with normal platelet and white cell counts, normal plasma proteins and serum protein electrophoresis. Further studies revealed increased concentrations of κ and λ light chains in a ratio of 34.89; a bone marrow biopsy found 12% plasma cells. Serum protein electrophoresis revealed no spike. ANCA, anti-glomerular basement membrane, antineutrophil antibody, hepatitis panel and serum complements were normal. A kidney biopsy result showed chronic sclerosing PICGN plus tubular necrosis, severe tubular atrophy, interstitial fibrosis and severe arteriosclerosis. Congo red stains were negative and electron microscopy showed no intraglomerular deposits. The patient was subsequently treated for myeloma with bortezomib and dexamethasone with good hematologic response but never recovered renal function. She remains on outpatient hemodialysis. Renal manifestations of myeloma often involve glomerular deposition disease, tubulointerstitial disease, with characteristic proteinaceous casts, or both. In contrast, our patient demonstrated neither of these findings but had chronic sclerosing PICGN. Crescentic glomerulonephritis occurring in patients with plasma cell dyscrasias has been previously reported, but the association remains extremely rare.

Metabolic Acidosis: Physiology, Presentation, and Diagnosis

Uncomplicated metabolic acidosis (MA) is characterized by hypobicarbonatemia with low serum pH. The overproduction of ketoacids, lactic acid, or pyroglutamic acid, the ingestion of ethanol, methanol, ethylene glycol, paraldehyde, or salicylates, and the retention of fixed acid in renal failure cause MA with increased anion gap (AGMA). Diarrhea, ammonium or acid ingestion, and renal tubular acidosis (RTA) cause metabolic acidosis with normal anion gap (NAGMA). In proximal RTA the proximal tubule fails to reabsorb filtered bicarbonate normally and bicarbonate wasting develops. Proximal RTA is most often seen as part of the De Toni–Fanconi syndrome. Causes include hereditary conditions and drug toxicity. Distal RTA is marked by inability to lower urine pH normally or by diminished ammonium excretion. Distal RTA can be further characterized by the measurement of serum potassium, renin, and aldosterone levels. Causes of distal RTA include drugs, interstitial renal nephritis, hereditary diseases, low mineralocorticoid levels, and urinary tract obstruction. The diagnosis of MA in mixed acid–base disorders is more complicated. Diagnosis here involves the use of acid–base nomograms or equations to estimate the normally expected physiological compensation and also involves the comparison of changes in anion gap with changes in bicarbonate concentration.

Carcinoma of the lungs causing enlarged kidneys.

Bilateral enlarged kidneys can be caused by a number of conditions. Renal metastasis is included in the differential diagnosis. We report a case of a 67-year-old woman with a 6-month history of productive cough and unintentional weight loss. Cavitary pulmonary lesions and bilateral enlarged kidneys were noted on imaging studies. Hematuria, azotemia, and proteinuria were present. Renal biopsy showed squamous carcinoma cells invading normal-appearing glomeruli and atrophic tubules. The invasive squamous cells stained negative for CK7 and CK 20. Lung biopsy confirmed squamous cell carcinoma. Our case shows that in patients with renal enlargement, even with the absence of a focal mass, renal metastasis should be considered, especially in those with suspected or diagnosed malignancy elsewhere.