DDAVP-associated hyponatremia.

More than 250,000 patients with nocturnal enuresis have been treated with DDAVP in the United States since 1989. It adequately controls nocturnal enuresis in over half of patients with significant improvement in their quality of life. Although the overall incidence of adverse effects associated with treatment of nocturnal enuresis with DDAVP is low, it is not a benign drug particularly when used in patients at extreme of age. A review of the literature and the present case demonstrate that the potential risk factors for hyponatremia following administration of DDAVP include hepatic disease, surgery, stress, pain, renal disorder, excessive fluid intake, and increased dose of DDAVP. Potentially serious side effects of DDAVP administration such as hyponatremia and seizure may be prevented by close monitoring of serum electrolytes, urine output, as well as fluid restriction and avoidance of solutions with low-sodium content.

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.

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.

Evidence for distal tubular inhibition of calcium efflux by nisoldipine in the SHR rat.

Nisoldipine, a calcium channel blocking agent, is known to have antihypertensive, renal tubular and hemodynamic effects. The present studies were designed to examine the effects of this drug on the renal tubular transport of calcium in 12 saline-loaded SHR rats. Calcium-45 was infused into three different nephron segments: early proximal, late proximal and early distal sites with or without nisoldipine. Calcium efflux averaged 93.6 +/- 4.9 and 90.5 +/- 8.7% after early and late proximal administration, respectively, indicating that the proximal tubule and the loop of Henle are highly efficient in transporting calcium out of the tubule. In distal nephron segments, calcium transport was limited to 41.1 +/- 4.8% of the amount delivered to these tubules. Nisoldipine inhibited the efflux of simultaneously infused calcium. This apparent inhibitory effect occurred predominantly in distal nephron segments where the drug reduced calcium efflux from 41.1 +/- 4.8 to 22.5 +/- 2.7%, indicating a 45.3% reduction in net calcium reabsorption. The results are consistent with the interpretation that nisoldipine-induced reduction in the tubular efflux of calcium was secondary to a direct inhibition of voltage-sensitive, L-type calcium channels or to a blunting of the rate of phosphorylation of channel proteins by protein kinase C in the distal tubular epithelial cells.

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.

The Medication Reduction Project: combating polypharmacy in South Dakota elders through community-based interventions.

The Medication Reduction Project (MED RED) is a community-based program addressing polypharmacy issues in elders. Using educational presentations and one-on-one medication reviews conducted by a pharmacist specializing in geriatrics, MED RED reached over 1,100 older adults in rural and urban southeastern South Dakota communities during 1993. Analysis of the longitudinal data indicate that older adults participating in one-on-one reviews were on fewer medications, had dosage reductions, were more likely to take their medications as directed, and increased their use of non-pharmacological alternatives. These elders also reported feeling better, spent less money per month on medications, and offered indications of improved functioning and increased levels of independence. These findings suggest that education about medication use is a dynamic tool in empowering community-based older adults to be assertive participants in their own health care.

Malnutrition in the elderly. Is it simply a matter of not eating enough?

Malnutrition is a common finding in elderly patients, especially at hospitalization. In those whose nutritional status is borderline, the stress of illness may bring about deficiency. Failure to correct malnutrition delays recovery and prolongs hospital stay. Inadequate intake is only one of many causes of nutritional deficiency in the elderly. Traditional height-weight tables are inexact in the elderly. To increase diagnostic accuracy in suspected malnutrition, several methods should be used (eg, calculation of weight loss over time; muscle mass-height comparisons; biochemical and hematologic measurements). After daily energy needs are determined--according to metabolic, activity, and stress expenditures--the best method of nutritional replacement must be determined. Enteral supplementation is the first choice because it sustains the integrity of the gastrointestinal tract. However, delaying implementation of parenteral nutrition when it is required is a common error that should be avoided. Continued supplementation is often needed after discharge. Depending on the health status of the patient, nutritional support can range from temporary admission to a skilled-nursing or extended-care facility to home supplementation through such programs as Meals on Wheels.

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.

MealMate: improving the nutritional status of elders using a milk-based nutritional supplement.

MealMate was a longitudinal research project conducted by the staff at the Geriatric Health Institute, a joint venture between Sioux Valley Hospital and the University of South Dakota School of Medicine. During Fall 1994, 64 older adults enrolled in this nutrition study at a Sioux Falls congregate dining site and drank a half-pint of whole milk combined with Carnation Instant Breakfast daily for one month. Pre-test and post-test data collected included anthropometric measures, specific blood tests from a venipuncture blood draw and use of standardized instruments to assess nutritional risk, depression, mental status and general demographic information. Results suggest that a longitudinal study with elders can be done effectively (attrition rate of less than 11%). While elders were very healthy at the onset, they nevertheless showed improved nutritional status over time. Laboratory tests showed significant increases in Vitamin D levels in adults over age 79. Using a more malnourished, home-bound sample of elders over age 79 and adding only whole milk to their diets are discussed as possible considerations for future research.

Renal hemodynamic effects of chronic ketorolac tromethamine treatment in aged lean and obese Zucker rats.

Ketorolac tromethamine is a relatively new non-steroidal anti-inflammatory drug (NSAID), with potent analgesic activity. Similar to other NSAIDs, ketorolac has the potential to impair renal function. To assess the renal hemodynamic impact of the ketorolac in aged lean and obese rats, ketorolac was orally administered to 46-week-old lean and obese Zucker rats for two weeks. Ketorolac was mixed with rat chow in a manner to provide a dose equivalent to 15 mg/kg body weight/day. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured under anesthesia by standard inulin and p-aminohippuric acid clearance method, respectively. Urinary prostaglandin (PG) E2 excretion was measured before and after ketorolac treatment. Ketorolac treatment significantly reduced obese rat GFR (0.47 +/- 0.08 vs 0.78 +/- 0.03 ml/min/g, p < 0.002) and ERPF (1.12 +/- 0.14 vs 2.36 +/- 0.26 ml/min/g, p < 0.001) relative to obese control rats. In comparison, ketorolac did not significantly alter lean rats GFR (0.77 +/- 0.04 vs 0.91 +/- 0.06 ml/min/g) or ERPF (1.92 +/- 0.20 vs 2.48 +/- 0.15 ml/min/g) relative to lean control rats. Chronic ketorolac treatment significantly reduced hematocrit by 20 and 30 percent in lean and obese rats relative to controls, respectively. The renal vascular resistance was significantly increased with ketorolac treatment in obese rats (36 +/- 4 vs 79 +/- 14 mmHg/ml/min, p < 0.001) but not lean rats (28 +/- 3 vs 38 +/- 5 mmHg/ml/min, NS) relative to corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal hemodynamic and histological consequences of diets high in unsaturated fat, protein or sucrose in obese Zucker rats.

The objective of this study was to determine the long-term effect of different dietary macronutrients on renal hemodynamics in obese Zucker rats. Female obese (fa/fa) Zucker rats were allowed to eat control chow (ObCL) or diets high in unsaturated fat (ObHF), protein (ObHP) or sucrose (ObHS) for a period of 24 weeks. Lean chow fed (LnCL) Zucker rats served as lean controls. After 24 weeks of dietary treatments, glomerular filtration rate (GFR, ml/mg/g, mean +/- SE) of ObHP and ObHS (0.38 +/- 0.06 and 0.27 +/- 0.05) rats were significantly (p < 0.005) lower than ObCL (0.74 +/- 0.05) and ObHF (0.88 +/- 0.1) rats. In a similar manner, the effective renal plasma flow (ERPF, ml/min/g) was significantly (p < 0.005) lower in ObHP and ObHS (1.28 +/- 0.16 and 1.04 +/- 0.2) than ObCL (2.46 +/- 0.31) or ObHF (2.85 +/- 0.25) rats. The ObHF rats appeared "protected" since they had similr GFR and ERPF but less proteinuria and glucosuria than ObCL rats. Histological examination of renal tissue from ObHP and ObHS fed rats revealed significant (p < 0.005) increase in sclerosis relative to ObCL rats. The sclerosis of renal tissue in ObHF was minimized and was found to be similar to ObCL rats. The mean arterial pressure and heart rates were similar in all dietary treated obese Zucker rats. When comparing obese and lean controls, ObCL rats had significantly (p < 0.03) lower GFR (0.74 +/- 0.05 vs 0.92 +/- 0.05) but similar ERPF (2.46 +/- 0.3 vs 2.82 +/- 0.12) than LnCL rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Systemic factors and renal hemodynamic effects of high-protein meal versus low-protein meal in conscious dogs.

The effects of a high-protein (HP) and low-protein (LP) meal on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal vascular resistance (RVR) were examined in conscious dogs. Ingestion of the HP and LP meal produced a temporary increase in systemic hemodynamic parameters due in part to a 'cephalic phase' of sympathetic excitement. However only the HP significantly altered renal hemodynamics, i.e. GFR, ERPF and RVR. Plasma renin activity (PRA), serum aldosterone and plasma atrial natriuretic peptide (ANP) concentrations were not significantly altered by either a HP or LP meal. Of all the serum electrolytes measured, serum Ca2+ concentrations were significantly lower after a HP meal. It would appear that protein-meal-induced changes in renal hemodynamics are independent of changes in systemic hemodynamics. The exact mechanism of action of a HP meal on renal hemodynamics is not clear, but it appears that one mechanism by which a HP meal may alter renal hemodynamics is by altered calcium homeostasis.

High-calcium diet in spontaneously hypertensive rats: intervention with calcium antagonist verapamil.

A number of studies have shown an antihypertensive effect for high-calcium diets, but others have found no effect or, even a prohypertensive effect. Because of these disparate results, studies were conducted in spontaneously hypertensive rats (SHR) fed either a normal calcium diet (1.0% calcium) or a high-calcium diet (4.0% calcium) with or without verapamil HCl (50 mg/kg body weight) from ages 5 to 12 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured by indirect tail cuff method. During the analysis of the electrolytes and vasoactive hormones monitored in this study, it was found that rats fed high-calcium diet had significantly elevated serum ionized and total calcium and calcium excretion. Systolic blood pressure for the verapamil-normal calcium diet (week 5, 148 +/- 4 mm Hg; week 7, 162 +/- 4 mm Hg) did not differ significantly from that of normal calcium diet (week 5, 152 +/- 2 mm Hg; week 7, 160 +/- 1 mm Hg). The high-calcium diet potentiated the development of hypertension, i.e., SBP was (157 +/- 2 mm Hg) on the 5th week and (174 +/- 4 mm Hg) on the 7th week. Conversely, verapamil high-calcium diet prevented the development of hypertension (week 5, SBP was 139 +/- 4 mm Hg; week 7, SBP was 146 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Post-obstruction diuresis: influence of renal prostaglandins.

The possible role of altered renal prostaglandin metabolism in the generation of post-obstruction diuresis (POD) was examined in 16 adult male Sprague-Dawley rats. Inhibition of cyclooxygenase by the administration of a combination of two nonsteroidal anti-inflammatory drugs (NSAID), meclofenamate and indomethacin in 8 of these rats exaggerated, rather than lowered the degree of natriuresis and diuresis that followed the release 24 h after bilateral ureteral ligation. Urine osmolarity was similar in the two groups of rats treated with the NSAID and vehicle. The results suggest an enhanced synthesis of renal vasoconstrictor and antidiuretic prostaglandins (thromboxane A2 or PGF2 alpha) during bilateral ureteral ligation. NSAIDs such as aspirin, indomethacin, meclofenamate and others may promote POD by blocking this prostaglandin pathway while promoting the cytochrome P450 monooxygenase pathway which may produce vasodilator, diuretic and natriuretic paracrine hormones. Additionally, inhibition of prostaglandin synthesis may have enhanced post-obstruction diuresis in the present studies by allowing a greater volume expansion during obstruction, as indicated by a reduced hematocrit in the rats that were pretreated with NSAID.