Noncompliance after kidney transplantation: a systematic review.

We performed a systematic review of the literature on medical noncompliance after kidney transplantation in the cyclosporine era. We wished to define commonalities that may help the clinician identify patients for early intervention. We found that patients who were at a higher risk of noncompliance after kidney transplants were younger, female, unmarried, and non-Caucasians. Patients who were recipients of living donor transplants and had been transplanted for a longer time with a history of a previous transplant were also at risk of noncompliance. We also found that patients displaying emotional problems, such as anxiety, hostility, depression, distress, lack of coping, and avoidant behaviors, were also at risk for noncompliance after kidney transplantation.

Gitelman's syndrome: report of a 19-year old woman with intractable hypomagnesemia and hypokalemia, and a review of the syndrome.

A case of refractory hypomagnesemia associated with hypokalemic alkalosis and hypocalciuria (Gitelman's syndrome) is described. The genetic mutations discovered to cause the hypokalemic alkalotic syndromes are described (the thiazide-sensitive sodium chloride co-transporter gene or TSC mutations in Gitelman's syndrome, and the sodium-potassium-chloride co-transporter gene or NKCC2 mutations in Bartter's syndrome). The molecular, electrolyte, and volume abnormalities are described, and the implications for diagnosis, therapy, and future research discussed.

Angiotensin-converting enzyme inhibitor use in older patients with heart failure and renal dysfunction.

OBJECTIVE: To examine the relationship between angiotensin-converting enzyme (ACE) inhibitor use and clinical outcomes among recently hospitalized patients with congestive heart failure (CHF) and coexisting renal insufficiency. DESIGN: A prospective cohort study. SETTING: Ten community hospitals in upstate New York. PARTICIPANTS: A total of 1076 hospital survivors identified from a consecutive series of CHF inpatients. MEASUREMENTS: Patients were followed prospectively for 6 months after hospital discharge to track mortality, hospital readmission, and quality of life. Clinical outcomes were stratified by ACE inhibitor use among those with renal dysfunction, defined as serum creatinine > or = 2.0 mg/dL, and among the remaining patients, whose serum creatinine was < or = 1.9. RESULTS: ACE inhibitor use was lower among 187 patients with renal dysfunction than among 889 patients with preserved function (41 vs 69%, P < .001). Age and sex were among the significant determinants of drug use in both groups. After adjustment for covariables, ACE inhibitor use among those with abnormal renal function was not associated with a lower risk for death or readmission, or better quality of life. By comparison, ACE inhibition conferred meaningful clinical benefit among those whose creatinine was < or = 1.9 mg/dL. CONCLUSION: Convincing evidence of clinical benefit from ACE inhibitor use is not readily detectable among a sample of 187 unselected older patients with CHF and moderate or severe renal insufficiency. Further studies to identify subsets of this group who might benefit are warranted.

Cure of Goodpasture's disease.

Goodpasture's Disease is an explosive multisystem disease presenting initially as a pulmonary-renal syndrome. There is often little margin for error in making an early correct diagnosis to avoid respiratory and renal failure. Complications of invasive diagnostic testing and aggressive immunosuppressive treatment often lead to other organ dysfunction due to infection, hemodynamic disturbances, fluid and electrolyte challenges, and nutritional deficiency. Artificial organ therapy is often needed for pulmonary and renal support, for immunomodulation, and for nutritional replacement. The outcome is often considered satisfactory if the patient survives the acute presentation. Persistent organ failure is quite often the case, especially renal failure. Quality of life is often improved if there is subsequent renal transplantation. By then the patient may be considered "cured". Two cases are described below, contrasting young and elderly white females both in previous good health who developed rapid onset of Goodpasture's disease. One was cured after transplantation, and one was cured without transplantation. The severity of the renal involvement was the same for both patients. Cure of Goodpasture's Disease in the native kidneys is uncommon; a review of the literature is provided.

Cerebral vasculitis associated with acute post-streptococcal glomerulonephritis.

The following is a case study involving a 13-year-old girl who presented initial symptoms of an upper respiratory infection. One week later she experienced a short seizure and hours later a grand mal seizure. MRI examination of the brain demonstrated multiple changing abnormal foci of increased density in white and gray matter suggestive of a vasculitic inflammatory pattern. As a result of proteinuria and red cell casts on urinalysis, a renal biopsy was performed resulting in a diagnosis of acute post-streptococcal glomerulonephritis (APSGN). We concluded on the basis of the MRI that vasculitis was secondary to APSGN. The following paper is a description of our findings in this case and a review of the literature supporting this new interpretation of CNS disease due to APSGN.

A case of 'reverse' pseudohyperkalemia.

Pseudohyperkalemia is diagnosed when the serum potassium level exceeds the plasma potassium level by 0.4 mmol/l. This is commonly encountered in settings of high leukocyte or platelet counts, since under these conditions, potassium, an intracellular cation, is released in supranormal amounts during the process of clotting. We report an unusual case wherein the reverse was true, i.e., the plasma potassium concentrations was higher than that found in the serum. Heparin, which is known to cause cell lysis, was used as the anti-coagulant in the plasma tubes. We propose that the underlying mechanism in this particular case is a heightened sensitivity to heparin-induced membrane damage in the face of a hematological malignancy.

Nutcracker syndrome: an underdiagnosed cause for hematuria?

Since its description in 1972, the Nutcracker Syndrome or Aorto-Mesenteric Left Renal Vein Entrapment Syndrome has been mentioned in the literature as an infrequent cause of hematuria originating from the left collecting system. It describes compression of the left renal vein in the fork between the abdominal aorta and the proximal Superior Mesenteric Artery (SMA), close to its origin. This results in left renal venous hypertension leading to the development of collateral veins with intrarenal and perirenal varicosities which can cause hematuria if the thin-walled septum separating the veins from the collecting system ruptures. The main presenting symptom is hematuria, with or without left flank pain. Some patients may present with left flank pain alone and, in a few, varicocele might be the only complaint. Exercise seems to aggravate the symptoms. It still remains unclear why compression of the left renal vein occurs in only a few patients despite its very peculiar course between the aorta and the SMA. Different anatomical details have been proposed. This controversy reflected itself on the lack of a clear agreement in regard to the treatment. We did a general overview of the current literature in an effort to elucidate further its pathophysiology. We present here three cases. The first case is that of a lady who presented with intermittent hematuria, sixteen years apart. Her hematuria cleared spontaneously without surgical intervention. Given her long symptom free interval, we strongly suspect some variable constitutional factors to play a role in the symptom development. The second case represents a perfectly healthy asymptomatic young women in whom an IVP done as routine renal donor work up revealed irregularities within the left collecting system that proved to be periureteric varices secondary to a nutcracker phenomenon as proved later by a renal angiogram. The third case describes a hypertensive, otherwise healthy, middle-aged male in whom an asymptomatic Nutcracker Phenomenon disclosed itself during a renal angiographic work up for his intractable hypertension. It is likely that the incidence of this anatomical problem is rather underestimated. We would like to emphasize the importance of its early inclusion in the differential diagnosis of left-sided hematuria because of the need for special testing for its diagnosis. Early proper diagnosis would spare many unneeded investigations.

Mitochondrial genome mutations and kidney disease.

Mutations in the mitochondrial genome have been shown to be responsible for several neuromuscular diseases in humans. In this article, we discuss the molecular genetics of mitochondria, their centrality in cellular energy production, and reasons why their genome is extremely vulnerable to mutation. Mitochondrial DNA (mtDNA) mutations and their classic encephalomyopathic clinical phenotypes are briefly reviewed, and evidence presented that mtDNA mutations also present primarily as kidney diseases. Research trends in the field are discussed. Suggestions are made regarding future work, the clinical implications thereof, and potential therapeutic utility accruing from these advances.

Effects of ketorolac tromethamine on erythropoietin levels in Sprague Dawley rats.

Ketorolac tromethamine (KT) is a potent analgesic, most often used in its injectable form postoperatively. Similar to other nonsteroidal antiinflammatory drugs (NSAIDs), it inhibits prostaglandin (PG) synthesis. Prostaglandins have been shown to be involved in the regulation of renal function as well as erythropoietin (Ep) production. The intent of this study was to determine the effect of KT on plasma Ep levels in Sprague Dawley (SD) rats. Twenty rats received either 15 mg/kg/d or the KT vehicle IM for 5d. Blood samples (1 ml) were collected via tail vein each day of treatment. Plasma Ep levels were significantly higher in the KT rats than normal controls with the greatest difference occurring on d4 of treatment (70.1 +/- 10.8 vs 30.9 +/- 10.84 mU/ml, p < 0.01). This change in Ep corresponded with a significant reduction in hematocrit (KT, 29.5 +/- 2.2 vs C, 40.8 +/- 2.2%, p < 0.01). Presence of fecal blood was noted in the KT treated rats. A similar second experiment was designed to determine if blood loss was the cause of altered Ep production. In this experiment controls (HC) were bled via tail vein, to match the hematocrits of KT treated animals. Repeated administration of KT led to a steady reduction in hematocrit. When compared, hematocrit matched animals showed no difference in plasma Ep levels on all days of treatment (KT, 48.0 +/- 4.9 vs HC, 44.6 +/- 3.1 mU/ml, N.S.). In conclusion, repeated administration of KT showed no impairment of Ep production and release in response to reduced hematocrit, suggesting that in this instance, prostaglandin inhibition plays a minimal role in Ep production or release.

Delivery dependence of early proximal bicarbonate reabsorption in the rat in respiratory acidosis and alkalosis.

In the intact rat kidney, bicarbonate reabsorption in the early proximal tubule (EP) is strongly dependent on delivery. Independent of delivery, metabolic acidosis stimulates EP bicarbonate reabsorption. In this study, we investigated whether systemic pH changes induced by acute or chronic respiratory acid-base disorders also affect EP HCO3- reabsorption, independent of delivery (FLHCO3, filtered load of bicarbonate). Hypercapnia was induced in rats acutely (1-3 h) and chronically (4-5 d) by increasing inspired PCO2. Hypocapnia was induced acutely (1-3 h) by mechanical hyperventilation, and chronically (4-5 d) using hypoxemia to stimulate ventilation. When compared with normocapneic rats with similar FLHCO3, no stimulation of EP or overall proximal HCO3 reabsorption was found with either acute hypercapnia (PaCO2 = 74 mmHg, pH = 7.23) or chronic hypercapnia (PaCO2 = 84 mmHg, pH = 7.31). Acute hypocapnia (PaCO2 = 29 mmHg, pH = 7.56) did not suppress EP or overall HCO3 reabsorption. Chronic hypocapnia (PaCO2 = 26 mmHg, pH = 7.54) reduced proximal HCO3 reabsorption, but this effect was reversed when FLHCO3 was increased to levels comparable to euvolemic normocapneic rats. Thus, when delivery is accounted for, we could find no additional stimulation of proximal bicarbonate reabsorption in respiratory acidosis and, except at low delivery rates, no reduction in bicarbonate reabsorption in respiratory alkalosis.

Metabolic acidosis stimulates bicarbonate reabsorption in the early proximal tubule.

The early proximal tubule is the major site for renal bicarbonate reabsorption but little is known about the influence of acidosis on transport in this segment. This study examined early proximal bicarbonate reabsorption in rats with chronic metabolic acidosis (MA) (induced by NH4Cl administration). Rats were studied by free-flow micropuncture techniques, after varying degrees of plasma volume expansion to vary the filtered load of bicarbonate (FLHCO3). At FLHCO3 less than 700 pmol/min, both control and acidotic animals reabsorbed greater than 80% of the filtered load by 2 mm from Bowman's space. At higher FLHCO3 (700-1,100 pmol/min), reabsorption in the early proximal tubule was significantly greater in MA rats vs. control (633 +/- 26 vs. 449 +/- 24 pmol/min, between 1 and 2 mm from Bowman's space, P less than 0.001). This MA-induced stimulation of early proximal bicarbonate reabsorption was completely reversed by restoring systemic pH to normal either by acute hypocapnia or alkali infusion. Thus bicarbonate reabsorption in the early proximal tubule correlated closely with changes in systemic pH in rats with MA when bicarbonate delivery was increased by plasma expansion. The mechanism of this effect remains to be determined.

Focal segmental glomerulosclerosis in patients receiving lithium carbonate.

Lithium carbonate is a commonly used psychiatric medication with a number of toxic renal effects, which include nephrotic-range proteinuria. A review of the literature concerning lithium-induced proteinuria is presented and three cases of nephrotic-range proteinuria are described in association with lithium therapy. The pathology in these three cases was focal segmental glomerulosclerosis, a finding not previously described.