Renal biopsy in connection with long-term treatment of psoriasis with cyclosporine

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CSA) therapy (range 2.5-6 mg/kg/day) of from six months to eight years. The study included pretreatment biopsies in 25 of the patients. After two years all biopsies shared features consistent with CSA nephropathy despite completely normal pretreatment morphology in 18 of the 25 patients. The severity of the findings, which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli, increased with length of therapy. Mild renal lesions were seen during the first two years. After four years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with the severity of the fibrosis. GFR studied in 14 patients six months to seven years after discontinuation of CSA was still significantly decreased in relation to baseline prior to therapy. The data from our study together with experiences from cardiac-transplanted patients indicate that patients with psoriasis, after two years therapy with CSA, should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.     

Is there an increased risk for tumor dissemination using ultrasonic surgical aspiration in patients with vulvar carcinoma?

Water diuresis after head trauma is most often due to central diabetes insipidus (DI). We report a patient with a history of a bipolar disorder and past lithium use who was noted to have polyuria and hypernatremia after head trauma. Inappropriate high sodium and volume replacement resulted in an increase in the polyuria. A lack of response to antidiuretic hormone/antidiuretic-hormone-like preparations led to the diagnosis of nephrogenic DI. The case illustrates the importance of calculating electrolyte-free osmolar clearance in the correction of hypernatremia. Persistence of the DI and mild renal impairment probably due to past lithium use are discussed.     

Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus

A 45-year-old man, with a 10-year history of manic depression treated with lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year history of polyuria and polydipsia, during which time urinalysis had been negative for glucose. After recovery from hyperglycaemia, he remained polyuric despite normal blood glucose concentrations; water deprivation testing indicated nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that when this man developed type 2 diabetes, chronic polyuria due to nephrogenic diabetes insipidus was sufficient to precipitate hyperosmolar dehydration.     

Desmopressin for the treatment of nocturnal polyuria in the elderly: a dose titration study

OBJECTIVE: To evaluate the decrease in nocturnal polyuria and the tolerability of three different doses of oral desmopressin in elderly subjects. SUBJECTS AND METHODS: Subjects were included in the study if they; (i) were healthy and free from medication with possible influence on their diuresis or voiding pattern: (ii) had an increased nocturnal frequency (> or = 2 nocturnal voids, as reported in the pre-screening period); and (iii) had a nocturnal urinary output of > or = 0.9 mL/min. Seventeen men and six women (mean age 68.1, SD 4.7 years) met these criteria and were treated with 0.1, 0.2 and 0.4 mg oral desmopressin given at bedtime, each dose taken for one week on three consecutive weeks. RESULTS: The mean (SD) nocturnal diuresis before treatment was 1.6 (0.7) mL/min, which decreased significantly to 1.1 (0.4) mL/min when 0.1 mg desmopressin was given. A dose of 0.2 mg desmopressin resulted in a further small decrease in the nocturnal diuresis to 0.9 (0.4) mL/min, whereas the 0.4 mg dose produced no additional effect. The reduction in nocturnal diuresis occurred almost exclusively in the group with a nocturnal urinary output of > or =1.3 mL/min. After treatment, diuresis returned to pretreatment levels. There was no change in body weight or in ankle circumference during desmopressin treatment and no serious adverse effects were observed. CONCLUSION: Desmopressin reduces nocturnal diuresis in polyuric elderly subjects and this reduction, occurring with doses of 0.1 mg given at bedtime, does not increase in a dose-dependent way.     

Renal side-effects of non-steroidal antirheumatic drugs

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are increasingly used for analgesia, as antirheumatics and to inhibit platelet aggregation. Renal side effects occur mainly in patients at risk, e.g. those with pre-existing renal insufficiency, or when used together with diuretics or a second NSAID. PATIENTS: In these patients, reversible impairment of renal function, disturbance of electrolyte homeostasis, edema and hypertension are quite common. Nephrotic syndrome with or without interstitial nephritis and renal failure is a rare complication of long-term NSAID therapy. Analgesic nephropathy may result from chronic NSAID use. These three renal complications are exemplified by case reports. CONCLUSIONS: Since side effects of NSAIDs are initially reversible, careful observation of patients can prevent chronic illness. Only rarely dialysis or treatment with glucocorticoids is indicated in patients with interstitial nephritis. Given the large number of patients taking NSAIDs, however, renal side effects are rare, and usually have no long-term consequences. Nevertheless, early detection of side effects is of importance for the prevention of long-term medical complications.     

Aneurysm clips: evaluation of MR imaging artifacts at 1.5 T

PURPOSE: Endothelin-1 (ET-1), a peptide produced by the vascular endothelium, causes profound renal vasoconstriction by binding to ET-A receptors. The present study examined the renal actions of ET-1 after ET-A receptors were blocked by BE-18257B to unmask the functions of ET-B receptors. MATERIALS AND METHODS: Renal hemodynamics and clearance measurements were obtained in anesthetized dogs after intrarenal infusion of BE-18257B at 100 ng./kg./min. (Group 1), after intrarenal infusion of ET-1 at 2 ng./kg./min. (Group 2), or after intrarenal infusion of ET-1 superimposed on BE-18257B (Group 3). RESULTS: In Group 1, BE-18257B infusion did not alter arterial pressure, renal blood flow (RBF), GFR or tubular function. In Group 2, ET-1 infusion led to a significant decrease in RBF and GFR (37 and 40%, respectively) without altering arterial pressure. Urinary volume and sodium excretion were not changed but osmolality decreased significantly. In Group 3, BE-18257B infusion significantly attenuated the decrease in RBF caused by ET-1 and increased GFR by 40% without altering arterial pressure, associated with significant diuresis and natriuresis. CONCLUSION: Renal vasoconstriction caused by ET-1 is attenuated by ET-A receptor blockade with BE-18257B, which unmasks the hemodynamic and tubular actions of ET-B receptors. As a result, it limits the ET-1 induced decrease in RBF and raises GFR, and leads to a diuresis and natriuresis.     

Detection of Epstein-Barr virus DNA in renal tissue from patients with interstitial nephritis

In order to demonstrate whether Epstein-Barr virus (EBV) infection might play a role in the pathogenesis of interstitial nephritis as suggested by many scholars, EBV DNA was detected in twelve specimens of frozen renal biopsy tissue from patients with interstitial nephritis by using nest polymerase chain reaction (nest PCR). For comparison, frozen renal biopsy tissue from ten patients with minimal change disease was used as control. Southern blot hybridization was used to check the specificity of PCR product. The results showed that eight of twelve frozen renal biopsy specimens from interstitial nephritis patients were EBV DNA positive (66.7%), as compared with negative in all the ten frozen renal specimens from minimal change disease patients. The differences was statistically significant (P < 0.01). The study strongly suggests that EBV infection may play an important role in the pathogenesis of interstitial nephritis. The location of EBV in renal tissue and the mechanism inducing interstitial nephritis by EBV are to be clarified.     

The renal factor in the post-traumatic "fluid overload" syndrome

Hypervolemia with hypertension often occurs 36-72 hours following massive blood and fluid replacement for hypovolemic shock. This syndrome of "fluid overload" has been attributed to the rapid intravascular flux of previously sequestered fluid in patients with impaired diuresis. This hypothesis was tested in 35 injured patients who received a mean of 9.3 L of blood and 17.4 L of salt during resucitation. The renal parameters measured soon after resuscitation included: 1) renal clearance of inulin (GFR), para-amino hippurate (ERPF), milliosmoles, sodium, and free water; 2) inulin space, renal vascular resistance (RVR), O2 consumption, renin, renal blood flow (RBF), and response to furosemide. Eighteen patients developed hypertension, hypervolemia, and respiratory insufficiency. When compared to the 17 normovolemic, non-hypertensive patients, the 18 hypervolemic patients had significantly increased RVR, with a significant decrease in RBF despite an increase in plasma volume and cardiac output. Furosemide produced less diuresis and natriuresis in the hypertensive patients. The balance between hypovolemia and "fluid overload" seemed percarious in the hypertensive patients. Peripheral renin and catecholamine levels were normal in both groups. Patients with post-traumatic "fluid overload" appear to have a combination of hypervolemia, respiratory insufficiency, hypertension, increased cardiac output, decreased extracellular fluid space, and decreased renal perfusion. These findings suggest that decreased interstitial fluid space compliance rather than "fluid overload" is the underlying factor leading to respiratory insufficiency. The therapeutic aspects of these findings are discussed.     

Renal manifestations in sarcoidosis

Clinically distinct renal disease is said to be rare in sarcoidosis, but autopsy reveals an incidence of renal involvement is 23 or 26% in Japanese studies. There are three categories of renal disease in sarcoidosis: 1) renal changes by abnormal calcium metabolism, 2) interstitial nephritis or granulomatous nephritis and 3) glomerulonephritis. Some investigators add renal angiitis to the three categories. In some patients without clinical renal disorders, renal involvement is discovered by chance at the time of autopsy or renal biopsy. Renal disease may develop during the course of sarcoidosis, preceding the diagnosis of sarcoidosis, or may be found simultaneously with extrarenal involvements at the time of diagnosis. Renal involvement should always be considered for exact diagnosis and appropriate treatment.     

Chronic interstitial nephritis and mesalazine: 3 new cases?

We report three new cases of chronic interstitial nephritis occurring in two patients with Crohn's disease and one patient with ulcerative colitis treated with mesalazine. In the three cases asymptomatic renal disease was revealed by an increase in serum creatinine which was normal before treatment. Renal biopsy showed features of severe chronic interstitial nephritis. Mesalazine withdrawal and administration of steroids in two cases led to partial improvement of renal function. Mechanism of renal toxicity of mesalazine is unknown. These observations stress the need for monitoring renal function in patients with inflammatory bowel disease treated with mesalazine.     

Evaluation of glomerular filtration rate by camera-based method in both children and adults

We describe a method to evaluate glomerular filtration rate (GFR) in both children and adults using 99mTc-diethylenetriamine pentaacetic acid (DTPA) and a gamma camera. METHODS: Renal scintigraphy with 99mTc-DTPA was performed in 40 children and 92 adults with various degrees of renal function. The percent renal uptake at 2-2.5 min after tracer arrival in the kidney was determined with background subtraction and correction for soft-tissue attenuation and was correlated by linear regression analysis with GFR measured from two blood samples. A perirenal region of interest was used for background subtraction. Renal depth was computed using the equations determined or validated on the basis of CT measurements, and the attenuation coefficient was set at 0.12. The obtained regression equation was used to predict GFR. Renal function was also assessed by the Gates' method. RESULTS: Percent renal uptake was closely correlated with GFR normalized for body surface area in all patients (y = 15.958x - 2.94; r = 0.939). GFR was successfully predicted using the regression equation in both children and adults. Gates' method severely overestimated GFR in children and provided less accurate values even in adults than our method. CONCLUSION: The method presented here requires neither blood sampling nor additional imaging and allows estimation of GFR in both children and adults.     

Early measurement of interstitial fibrosis predicts long-term renal function and graft survival in renal transplantation

This study investigated the relationships between renal allograft interstitial fibrosis, renal function and graft survival. A total of 107 consecutive renal transplant recipients immunosuppressed with cyclosporin were studied. Needle core transplant biopsies were performed before operation and at 1, 6 and 12 months after transplantation. Allograft fibrosis was assessed by histomorphometric analysis of graft interstitial volume fraction. Renal function was measured by isotopic glomerular filtration rate (GFR) measurement at the same time points. Interstitial volume fraction was already high in preperfusion biopsies, significantly increased with time but stabilized at 6 months after transplantation. GFR correlated negatively with interstitial volume fraction at 6 months (P = 0.05). Interstitial volume fraction at 1 month was not a useful predictor of subsequent graft survival but for allografts surviving to 6 months an interstitial volume fraction above 25 per cent predicted significantly poorer survival (P = 0.04). It provides an objective measure of chronic allograft damage and may prove to be a useful surrogate endpoint in the study of therapeutic intervention.     

Impaired kidney function in lithium therapy

Long-term therapy with lithium may be associated with a broad spectrum of functional and structural side-effects in the kidney. Among these features, nephrogenic diabetes insipidus is the most frequent and it can be expected to occur in 20-70% of the patients. Diabetes insipidus is the result of a lithium induced resistance of collecting ducts to antidiuretic hormone. Additional functional disturbances are represented by renal tubular acidosis and consequences of hypercalcemia. Structural alterations of the kidney have a rare occurrence. In the literature, there are accounts of chronic tubulo-interstitial nephritis, acute tubular necrosis and few cases of glomerulopathies. Our report of a patient with chronic interstital nephritis is supplemented by a brief discussion of the diverse picture of the nephrotoxicity of lithium.     

Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients

Quinine-induced acute renal failure attributed to the hemolytic-uremic syndrome has been infrequently reported. A case of acute renal failure due to acute interstitial nephritis associated with ingestion of quinine and the subsequent response to steroid therapy is described.     

Gay men who engage repeatedly in unprotected anal intercourse with casual partners: the Sydney Men and Sexual Health Study

A probable outbreak of oak (Quercus calliprinos) toxicosis in a herd of beef cattle--heifers and first-calving cows--grazing in the Judean foothills of Israel is described. Toxicosis probably occurred because of the consumption of oak leaves and buds during a period of pasture scarcity without any feed supplementation. A progressive syndrome of wasting, dullness, anorexia, polyuria, nephrosis, constipation and recumbency, culminating in death, was seen. A high mortality rate of 83% (38/46 animals) was noted. The clinical-pathological findings revealed increases in blood urea, creatinine, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK), lactate dehydrogenase (LDH) and inorganic phosphorus. Decreases were found in alkaline phosphatase (ALP), total serum protein, albumin (ALB), triglyceride (TG), calcium (Ca), magnesium (Mg), sodium (Na) and chloride (CI). The main pathological findings were severe nephrosis, chronic interstitial nephritis, and occasional intestinal ulceration. On the basis of epidemiology, clinical signs, clinical-pathological and pathological findings and renal histology, a tentative diagnosis of oak toxicosis was made.     

ACV synthetase: expression of amino acid activating domains of the Penicillium chrysogenum enzyme in Aspergillus nidulans

A 51-year-old woman developed an acute onset of renal dysfunction accompanied by rash, lumbar pain, arthralgias, fever, eosinophiluria, and an elevated serum creatinine after 6 days of intravenous piperacillin-tazobactam therapy. On discontinuing piperacillin-tazobactam and after a 21-day course of prednisone, the patient's constitutional symptoms dissipated and her renal function returned to baseline. Acute interstitial nephritis has been reported as an adverse effect of many drugs, including antibiotics, but not, to our knowledge, after piperacillin-tazobactam. The time course of events suggested that piperacillin-tazobactam was the cause of acute interstitial nephritis in this patient.     

MDS and AML with trisomy 8 as the sole chromosome aberration show different sex ratios and prognostic profiles: a study of 115 published cases

There are few studies on the use of dihydropyridine calcium antagonists in hypertensive patients with moderate renal insufficiency. We undertook an open study on the effects on renal function, albumin excretion and blood pressure of the slow-onset, long-acting dihydropyridine calcium antagonist, lacidipine, in 14 patients with stable, chronic renal insufficiency (mean assessed GFR 0.78 ml/s, range 0.50-1.17 ml/s) and moderate hypertension. Following a 2 week washout phase, lacidipine was administered for 24 weeks in a dose of 2 mg/day with the dose being titrated at 2 weekly intervals to a maximum of 6 mg/day in order to achieve adequate blood pressure control. Frusemide was introduced if blood pressure was not controlled on the maximum lacidipine dose. Blood pressure, creatinine clearance, 24 h urinary albumin excretion and plasma creatinine and albumin concentrations were measured at regular intervals throughout the study. Isotopic GFR was determined at the end of the washout period and at week 24. Lacidipine was not very effective in controlling blood pressure and had an adverse effect on renal function. In 3 patients with an incipient nephrotic syndrome this necessitated withdrawal from the study. Mean GFR of the 10 patients who completed the study decreased from 0.69 ml/s/1.73 m2 at baseline to 0.56 ml/s/1.73 m2 at week 24 (p = 0.006) with a decline in GFR being observed in 9 of these patients. The decrease in GFR was greatest in patients with poorly controlled blood pressure. An insignificant increase in mean urinary albumin excretion occurred during the study with this increase being observed only in patients with albuminuria > 1 g/24 h at baseline. These findings indicated that systemic hypertension altered glomerular hemodynamics and that the vasodilatation of pre-glomerular vessels which followed introduction of the calcium antagonist may have exacerbated this situation. The withdrawal of an angiotensin converting enzyme inhibitor during the washout period may have contributed to these changes. We suggest that renal function should be monitored closely in patients with renal insufficiency when a calcium antagonist is being used to control blood pressure, particularly in those with either marginal blood pressure control, significant albuminuria or an incipient nephrotic syndrome.     

Lack of sensitization to the effects of d-amphetamine and apomorphine on sensorimotor gating in rats

Haemolytic-uremic syndrome (HUS) is the leading cause of acute renal failure in the childhood. It is characterised by microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure and injury of the renal microvascular endothelium. In HUS the condition of proteolytic kallikrein-kinin system is unknown. The renal KKS seems to participate in the regulation of blood pressure, control of sodium and water excretion, renal vascular resistance and renin release. In this study the role kallikrein in the developing HUS was studied. The general activity of kallikrein in plasma and urine was determined by trypsin-like peptidohydrolase activity (TP), which was measured using substrate Z-D-Ala-Leu-Arg-pNa. Chymotrypsin-like protease activity (ChP) was measured using substrate Glp-Ala-Ala-Leu-pNa. Clinical data were analysed on 60 pediatric patients with HUS, 29 girls and 31 boys, ranging in the age from 3 months to 11 years. TP and ChP levels were determined in different periods of HUS (anuria, diuresis beginning, polyuria, recovery) in serum and urine. In acute phase TP and ChP activities increased significantly. In diuresis recovery serum TP activity was higher, but urine TP level became normal. In dynamic serum and urine ChP levels had tendency to decrease. The present work showed that TP and ChP levels demonstrated activity of pathological renal process and condition of glomerules.     

Acute renal failure--etiologic and therapeutic considerations. A five-year experience at a single institution

In the present study we highlight the epidemiology, etiologic spectrum, and evaluation of ARF in adults. We then expand on the pathophysiologic mechanisms of renal failure and discuss the rationale for current therapeutic strategies in ARF patients. A total of 79 patients (45 male, female 34), aged 18-75 years (median age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years (January 1990 through October 1995). Emergency hemodialysis sessions following an acute anuric episode were instituted in 39 cases (49.3% of all patients). The median number of hemodialysis procedures per patient treated at our institution was 3.2 +/- 1.9. The total number of acute interstitial nephritis-associated ARF was 40. In 30 of them (75%) the acute renal insult included a combination of several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted from a combined therapeutic regimen and in the remaining 5 (12.5%) from the application of a single drug. Acute interstitial nephritis developed in 2 patients following a viral infection. In the hemodialysis-treated ARF group 12 patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented with renal impairment for an unspecified period of time preceding the development of overt ARF. In a subset of this group of patients, ARF occurred in 7 patients (17.95%) following an urologic intervention, in 8 patients (20.51%) as a consequence of thermal or mechanical trauma or intoxication and in 3 cases (7.69%) it resulted from fever of unknown origin. Three patients with postoperative peritonitis and 4 other (10.26%) with postoperative complications were encountered in our series. No cases of septic abortion-related or obstetric-related ARF were recorded. 92.3% of all hemodialysis-treated patients seen at our Institution had received a combination of antibiotics and only 2 patients had been pre-treated with a single antimicrobial agent. Our results underscore the strong tendency towards diversity in the etiologic spectrum of clinical entities causing ARF and the increase in the number of acute interstitial nephritis. These factors highlight the importance of precise dosing and administration of drugs, especially antibiotics, as well as the duration of antibiotic treatment.     

The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and C(Li) was 88% (P < 0.01) of the baseline values, APR and FPR had not changed significantly, and potassium clearance was significantly decreased. Through the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients randomized to treatment with conventional antihypertensive drugs (n = 35), C(Li) was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant (P < 0.05). An unchanged or increased APR in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P < 0.01), whereas the clearances of immunoglobulin G and retinol-binding protein were unchanged in this group. In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional antihypertensive therapy. During ACE inhibition, the reabsorptive capacity of the proximal tubule appeared to be better preserved, which might be of importance for the beneficial effect of this treatment in chronic renal disease.