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Transient neonatal hyperkalemia in the antenatal (ROMK defective) Bartter syndrome.

OBJECTIVE: Identification of neonatal hyperkalemia as a complication of Bartter syndrome (BS), a disorder usually characterized by hypokalemic metabolic alkalosis. Study design Case-series description of a group of 12 infants with mutations in the renal potassium channel ROMK, causing one of the antenatal variants of BS. RESULTS: Prematurity, postnatal polyuria, and dehydration were seen in all cases. Plasma potassium was as high as 9.0 +/- 1.2 mmol/L and sodium as low as 124 +/- 3.5 mmol/L, appearing usually at day 3 of life and normalizing by the end of the first postnatal week. No hyperkalemia was found in 12 neonates with the variant of BS and deafness. The mean plasma potassium level during the first week of life among a group of very low-birth-weight infants with similar relative azotemia was 4.9 +/- 1 mmol/L (P <.001). The postneonatal period in the ROMK-defective children with BS was characterized by failure to thrive, hypercalciuria, nephrocalcinosis, and minimal-to-no hypokalemia. CONCLUSIONS: Early postnatal hyperkalemia, sometimes severe, may complicate antenatal BS associated with ROMK mutations. Its association with hyponatremia and hyperreninemic hyperaldosteronism may erroneously suggest the diagnosis of pseudohypoaldosteronism type 1. The expression of ROMK in both the thick ascending limb and cortical collecting duct may explain this apparently tubular maturation phenomenon.

Adolescent↗

Operative management of renovascular hypertension. Results after a follow-up of fifteen to twenty-three years.

From March 1960 through January 1968, 71 patients underwent operations for renovascular hypertension at our center. There were three operative deaths in 94 procedures. Primary nephrectomy was performed in 26 patients. Attempted revascularization of 62 kidneys was successful in 46 (74%). In 13 (87%) of the 15 cases considered operative failures, the patients underwent either secondary nephrectomy (11) or repeat revascularization (two). Based on the results of the final operation, initial blood pressure response (1 to 6 months postoperatively) in the surviving patients indicated 44% cured (30 patients), 40% improved (27), and 16% unchanged (11). The sequential clinical, functional, and anatomic follow-up evaluations to time of death or to date are available in 66 of the 68 patients (97%) who survived operation and form the basis of this report. Fifteen- to 20-year arteriographic follow-up in 16 patients revealed one late neointimal anastomotic stenosis and an additional three aortic suture line false aneurysms in Dacron aortorenal grafts. During this 15- to 23-year follow-up, 71% of atherosclerotic (AS) patients and 23% of fibromuscular dysplasia (FMD) patients died. Cardiovascular (CV) morbid events occurred in 77% of AS patients and in 19% of FMD patients. The cumulative incidence of death and CV morbid events during follow-up is examined by Kaplan-Meier life tables and Cox's proportional hazards regression analysis in these respective groups to identify preoperative markers predictive of longer event-free survival in relation to blood pressure benefit by operation (for example, focal vs. diffuse AS, presence of cerebrovascular disease, ischemic heart disease, left ventricular hypertrophy seen by electrocardiography, azotemia, smoking, diabetes, and hyperlipidemia).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Concomitant renal revascularization in patients undergoing aortic surgery.

Sixty-three patients who underwent renal revascularization at the time of aortic surgery were retrospectively reviewed. These patients had significant renal artery stenosis in addition to either severe aortoiliac occlusive disease or aortic aneurysmal disease. Fifty-eight patients were hypertensive, whereas five patients were normotensive and these renal lesions were treated prophylactically. The operative mortality rate was 3%. Despite lack of selectivity in these patients with diffuse atherosclerosis, 60% (35 of 58) of the patients with hypertension could be classified as either "cured" or "improved." Patients with bilateral renal artery involvement and moderate azotemia were noted to improve with respect to renal function postoperatively. No patient has required chronic dialysis at a mean follow-up period of 22.6 months. Simultaneous aortic and renal artery surgery may be performed with low morbidity and mortality rates and produce a gratifying improvement in hypertension. Renal functional improvement and perhaps preservation of renal mass may be anticipated in selected patients.

Adult↗

Simultaneous aortic reconstruction and renal revascularization: risk factors and late results in eighty-nine patients.

From 1973 through 1984, graft replacement of infrarenal aortic aneurysms (N = 56) or occlusive disease (N = 33) was performed in conjunction with simultaneous renal revascularization in 89 patients. Isolated renal artery stenosis was corrected by unilateral reconstruction in 56 patients (63%), but the remaining 33 (37%) had diffuse involvement that required either bilateral renal artery grafts or unilateral revascularization of solitary kidneys. The incidence of hypertension (greater than 180/90 mm Hg) refractory to preoperative medical therapy (88%), severe coronary disease documented by angiography (40%), and postoperative azotemia (33%) or oliguric renal failure (15%) was significantly higher among patients with bilateral renal artery disease (p less than 0.05). In addition, this group had twice the early mortality rate (15%) of patients having unilateral renal artery lesions (7.1%). During a mean follow-up interval of 37 months, medical control of hypertension was enhanced in 46 of the 80 operative survivors (58%), and renal function improved or remained stable in 63 survivors (79%). Five-year actuarial survival presently is 65% for the entire series, with a cumulative mortality rate of 38% among patients who underwent aneurysm resection (mean age 64 years) in comparison to 15% (p = 0.03) for those patients with aortoiliac occlusive disease (mean age 60 years).

Aged↗

Aortic clamping during elective operations for infrarenal disease: The influence of clamping time on renal function.

OBJECTIVE: Aortic clamping proximal to the renal arteries is sometimes necessitated during infrarenal and juxtarenal aortic surgery and may be associated with an increased risk of renal ischemia and its consequences. The aim of the study was to estimate this risk and possibly identify a "safe" duration of renal ischemia. METHODS: Medical records were retrospectively reviewed for 60 consecutive patients (from 1987 to 1994) with abdominal aortic aneurysm (n = 43) and occlusive disease (n = 17) confined to the infrarenal or juxtarenal aorta who underwent infrarenal aortic reconstruction with temporary suprarenal clamping. The data obtained included risk factors, preoperative and postoperative serum creatinine level, blood urea nitrogen (BUN) value, proteinuria before surgery, and suprarenal clamping times. RESULTS: The mean age of the patients was 64.4 years (+/- 11.4 years), and 74% were men. Concomitant cardiac disease was present in 41% of the patients, and 9% had diabetes. The preoperative creatinine level was 1.21 mg/dL (+/- 0.54 mg/dL), and the BUN value was 16.6 mg/dL (+/- 7.8 mg/dL). During surgery, blood flow to the renal arteries was interrupted for 32.0 minutes (+/- 17 minutes). None of the surviving patients needed dialysis or had signs of acute renal failure after the operations, but transient azotemia (rise in creatinine level) occurred in 23% of the patients. Risk factors for this condition were high preoperative creatinine values and hypotension during surgery, but the main determinant was total renal ischemia time. Odds ratios for such transient renal dysfunction showed as much as a 10-fold risk when suprarenal aortic clamping was greater than 50 minutes as compared with 30 minutes or less. CONCLUSION: Postoperative renal function impairment is rare in this group of patients. If suprarenal clamp duration (renal ischemia time) is brief, patients with normal preoperative creatinine levels exhibit no increase or a marginal increase in BUN or creatinine levels after surgery. Accordingly, suprarenal aortic clamping less than 50 minutes in this patient group appears safe and well tolerated.

Adult↗

The role of nitric oxide in radiation nephropathy.

Sufficient radiation will cause kidney injury with hypertension, azotemia, and death from renal failure. There is early endothelial injury after radiation, which could lead to a deficit of constitutive nitric oxide (NO) synthesis, with capillary thrombosis and hypertension, both of which are seen in radiation nephropathy. In a rat radiation nephropathy model, the serial evolution of urinary cyclic guanosine monophosphate (cGMP), a marker of kidney NO, was studied and a deficit in urinary cGMP was found. This radiation-induced cGMP deficit was prevented by high-dose Captopril treatment. Low-dose Captopril treatment protected against radiation nephropathy without preventing the decrease in urinary cGMP. An inhibitor of NO synthesis, L-N-arginine-methylester, did not blunt the beneficial effect of Captopril treatment. We conclude that there is a deficit in urinary cGMP in radiation nephropathy, but that prevention of this deficit is not essential in the prevention of radiation nephropathy by Captopril.

Animals↗

Animal model of diabetic nephropathy.

Injection of subtotally nephrectomized rats with streptozotocin produced metabolic abnormalities resembling diabetic nephropathy in humans. These abnormalities were hyperglycemia, hypoinsulinemia, azotemia, hypertriglyceridemia and hypercholesterolemia, accompanied with an increase in glycosylated protein. Extraordinary changes in the urinary excretion of glucose and protein were also observed in rats that received streptozotocin treatment after subtotal nephrectomy. In addition, the level of creatinine clearance was significantly decreased. The pathological findings in the kidney of these rats revealed lesions of the glomerular capillary loops, mesangial area and Bowman's capsule. Coagulation was also found in the glomerular capillaries. Our results suggest that this rat model would be useful for studies of diabetic nephropathy.

Animals↗

Renovascular hypertension. Changing concepts in management.

The current approach to renovascular hypertension at the Lahey Clinic Medical Center consists of wider application of revascularization procedures than was possible a decade ago. Surgery is more frequently advised in patients over 50 years of age, in patients with atherosclerotic disease, and in patients with azotemia to restore renal function. Revascularization is suggested in some patients with a totally occluded renal artery, and alternatives to aortorenal bypass are advocated when the aorta is diseased. Bench surgery is used when appropriate, and concomitant aortic replacement and renal revascularization are generally avoid.

Aorta↗

Respiratory manifestations of systemic disease. 3. Neurologic, skeletal, dermatologic, gynecologic, and gonadal diseases and disorders of pregnancy.

Many nonpulmonary diseases may present with respiratory manifestations or may involve the lungs later in the disease course. The mechanisms by which such involvement occurs are almost as diverse as the diseases themselves and include the following. Hematogenous spread of disease is one of the most common mechanisms of lung involvement, for example, lung involvement by metastatic malignant disease. Cytotoxic factors from another anatomic location may be deposited in the alveolar basement membranes and cause pulmonary damage, for example, pulmonary hemorrhage associated with Goodpasture's syndrome. The pulmonary vasculature may prominently manifest generalized disease, as frequently occurs in Wegener's granulomatosis. Toxins accumulated as a result of disease in another organ system may damage the alveolar capillaries and result in pulmonary edema, as can occur in patients with severe azotemia due to renal failure. Depletion of lung surfactant as a consequence of disease in another organ system may produce alveolar collapse and respiratory failure; a disease that can have this effect is acute pancreatitis. The lungs may be the first organs to exhibit, through unknown mechanisms, underlying systemic diseases such as the collagenoses. Humoral factors released in another anatomic site may cause pulmonary problems; for example, bronchospasm may develop in patients with carcinoid of the intestine as a result of serotonin released by the tumor. Injury to another organ system can produce lung damage by complex mechanisms; an excellent example is the occasional development of neurogenic pulmonary edema in patients with trauma to the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Diseases↗

Interstitial nephritis in a patient with Legionnaires' disease.

Renal involvement in legionnaires' disease is a well-known, yet incompletely understood, complication. Manifestations of renal involvement include proteinuria, hematuria, pyuria, cylindruria, and azotemia. Previous cases of legionnaires' disease with renal involvement have shown pathophysiologic changes consistent with acute tubulointerstitial nephritis or acute tubular necrosis. A toxic metabolite produced by Legionella pneumophila has been theorized to produce a vasoconstrictive effect on the renal microvasculature, leading to ischemia and renal dysfunction. The case reported here is unique in that the patient presented with interstitial nephritis in the absence of pulmonary signs or symptoms.

Adult↗

Extreme hyperkalemia induced by drugs.

Because of age and disease-induced pathophysiologic changes, elderly and diabetic patients are prone to hyperkalemia under even the best of circumstances. Further complicating the situation is the fact that the drugs often prescribed for these populations can affect potassium homeostasis. Drs Rigolin and Chap describe a case in which an elderly diabetic man with azotemia survived extreme drug-induced hyperkalemia.

Aged↗

Effects of hyperthermia on the rat bladder: a pre-clinical study on thermometry and functional damage after treatment.

The rat bladder was heated using a microwave applicator which was equipped with a system of circulating deionized water. The applicator was operated at 434 MHz and was placed at the ventral side with the rats in supine position. Temperatures in the bladder and adjacent were monitored using thermocouples with single or multiple sensors. One thermocouple located most centrally in the bladder served as reference. The rats were treated at intravesical reference temperature of 41, 42, 43, 44 and 45 degrees C for 1 h. The heating time to reach the reference temperature was approximately 5 min. Temperatures inside the bladder varied within 0.5 degrees C from the reference value, while the temperatures in the urethra were approximately 1.0 degrees C lower. At the left and the right side of the outer bladder wall, temperatures were approximately 0.5 degrees C lower than the reference value, while the temperature on the dorsal and ventral sides of the bladder wall were 1.0-1.5 degrees C lower. In the rectum, located in the treatment field, the temperature reached 39.1, 40.5, 42.4 and 42.5 degrees C after 1 h of hyperthermia at intravesical reference temperatures of 41, 42, 43, 44 and 45 degrees C, respectively. Body core temperature measured in the esophagus behind the pericardium never exceeded 40.0 degrees C. The capacity of the bladder was assessed after 1 h at 43, 44 and 45 degrees C at various intervals after heat treatment. In the sham treated control group and in the animals treated at 43 degrees C, no reduction in bladder capacity was observed. The treatment group where the bladder was kept at 44 degrees C for 1 h showed a clear reduction in bladder capacity at days 1 and 3 after hyperthermia. In the 45 degrees C treatment group, four out of seven rats died, this within a few days after treatment. The three surviving rats were tested for bladder capacity and all had a reduced capacity at days 3 and 7 post-treatment. Four weeks after 44 degrees C hyperthermia, all rats had recovered. After hyperthermia, depending on the heat-dose, an increase in blood urea nitrogen (BUN) was observed. After treatment at 42, 43 and 44 degrees C, peak values were observed after approximately 1 day (16 or 24 h) followed by recovery; after 42 degrees C, BUN levels were almost back to normal after 1 week; after 43 degrees C, the level was still twice as high as control levels; and after 44 degrees C, recovery of BUN levels to normal seemed slow, 1 week after treatment it was still five times as high as control. From these results, it is concluded that temperatures in the bladder below 44 degrees C are well tolerated. After 1 h at 44 degrees C, a transient decrease in bladder capacity was observed, as well as a high level of azotemia. After 1 h at 45 degrees C, a high mortality rate was observed. These observations agree with early clinical observations and may be used as guidelines for further clinical work.

Animals↗

Ribonucleases as a novel pro-apoptotic anticancer strategy: review of the preclinical and clinical data for ranpirnase.

Cytotoxic ribonucleases (RNases), such as ranpiranase, represent a novel mechanism-based approach to anticancer therapy. These relatively small proteins selectively attack malignant cells, triggering apoptotic response and inhibiting protein synthesis. Ranpirnase, originally isolated from oocytes of Rana pipiens, is a member of a family of endoribonucleases. The anticancer effects of ranpiranase have been documented in both in vitro and in vivo experimental tumor models. The effects of ranpiranase appear to be selective for cancer cells. Based on Phase I study data, the maximum tolerated dose (MTD) was 960 microg/m2, with the dose-limiting toxicity (DLT) characterized by proteinuria with or without azotemia, peripheral edema, and fatigue. Ranpirnase did not induce myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy, hepatotoxicity, or adverse metabolic effects. Phase II tumor-specific trials investigated the activity of ranpirnase in malignant mesothelioma, breast cancer, non-small cell lung cancer, and renal cell cancer. A Phase III randomized study in malignant mesothelioma patients compares the combination of ranpirnase plus doxorubicin to doxorubicin monotherapy.

Animals↗

Transient improvement of hypertension-induced chronic renal failure with mycophenolate mofetil treatment.

A young female with essential hypertension developed progressive azotemia; renal biopsy showed hypertensive nephrosclerosis with considerable tubulointerstitial disease and cellular infiltration. The addition of mycophenolate mofetil (MMF) to her antihypertensive treatment resulted in a dramatic improvement of renal function during the following three months. When the patient discontinued MMF treatment, end-stage renal failure rapidly developed. This patient represents the first report of the beneficial use of MMF in non-immune chronic renal disease and demonstrates that significant functional improvement may be obtained with the addition of MMF to the treatment of hypertensive nephrosclerosis for patients in whom there is significant tubulointerstitial inflammatory infiltration.

Adult↗

A middle-aged woman with back and flank pain.

Xanthogranulomatous pyelonephritis is an uncommon variant of chronic pyelonephritis that predominantly affects middle-aged women. Patients usually present with fever, back or flank pain, flank mass, and the constitutional symptoms of fatigue, malaise, weight loss, and anorexia. Rarely, they may present with a draining sinus. There is usually a history of urinary tract infection, obstruction, or instrumentation. Other abnormalities include anemia, leukocytosis, abnormal liver enzymes, pyuria, and hematuria. Mild azotemia may be present, but frank renal failure is rare. Urine and renal tissue cultures are frequently positive. The most commonly isolated bacterial pathogens are P. mirabilis and E. coli, but other organisms have also been implicated. A CT scan is the best radiologic imaging technique to discover the extent of inflammation as well as any involvement of adjacent structures. Lipid-laden macrophages called xanthoma cells characterize the disease at the microscopic level. Nephrectomy is curative. Careful preoperative evaluation will guide surgical planning in choosing an approach that provides adequate exposure of the affected tissue and facilitates subsequent care of the patient.

Back Pain↗

Role of quercetin on hepatic urea production in acute renal failure.

Acute renal failure (ARF) is a serious damage of renal function induced by various nephrotoxic drugs, ischemia, bilateral urethral obstruction, trauma and unilateral nephrectomy. Dramatic clinical syndrome, azotemia, develops as a result of hypovolemia, oliguria, reduced glomerular filtration and acidosis. In addition to classic medications recent studies give more attention to beneficial effect of natural plant products as bioflavonoids. We have studied the influence of bioflavonoid, quercetin, on hepatic urea production in glycerol induced ARF in the rats. Male Sprague Dawley rats were used in the experiment. The value of urea production in the liver was determined by measuring of liver arginase activity, the terminal enzyme of urea cycle. Arginase activity was increased (p < 0.01) as well as urea level (p < 0.001) 48 h after glycerol administration. Pretreatment by quercetin suppressed the arginase activity in the liver (p < 0.05) and plasma levels of urea (p < 0.01). So, we have concluded that quercetin may be beneficial in glycerol induced ARF.

Acute Kidney Injury↗

Combination of continuous renal replacement therapies (CRRT) and extracorporeal membrane oxygenation (ECMO) for advanced cardiac patients.

BACKGROUND: The critically ill patients may require mechanical ventilation, cardiac mechanical support, and other types of critical support. Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, which provides good cardiopulmonary and end-organ support. Continuous renal replacement therapies (CRRT) exhibit important advantages in terms of clinical tolerance and blood purification. This investigation aims to evaluate the acute renal failure in cardiac patients under ECMO, and assess the effect of combining these two technologies, ECMO and CRRT. METHODS: Between December 1998 and June 2001, 10 adult cardiac patients were treated on ECMO. Five of them were treated with both ECMO and CRRT. The clinical outcomes were retrospectively analyzed. RESULTS: Of the 10 patients studied, five were men and five were women. The mean age of survivors and non-survivors was 37.00 +/- 14.54 years and 46.17 +/- 7.41 years, respectively. The overall mortality rate was 60%. Survivors did not differ significantly from non-survivors in age or gender. The APACHE II scores on the first day of ECMO support between survival and non-survival were 19.00 +/- 9.38 and 24.67 +/- 3.50 (P value = 0.392) (Table 2), which demonstrates no significant differences too. The cause of death in most patients was related to organ system failure during the 24 h immediately before ECMO started. Five patients with acute renal failure treated by CRRT were eventually died. The median and mean survival in this group on CRRT was 40.50 +/- 18.07 h and 92.60 +/- 60.50 h. CONCLUSION: We conclude that mortality rate for acute renal failure in cardiac patients under ECMO continues to be high. Our data suggest that acute renal failure is generally a part of multiorgan failure. This unique form of acute renal failure, causes generalized edema and fluid overload despite still low serum creatinine and azotemia, and deteriorates rapidly to death. From this study shows, advanced cardiac failure may need more aggressive and early initiation of ECMO support before acute renal failure develops. Acute renal failure in advanced heart failure under ECMO support means a grave sign, need aggressive heart transplantation therapy as soon as possible. Combination of CRRT and ECMO might serve an alternative therapy bridging the temporary replacement treatment and heart transplantation in advanced cardiac patients.

APACHE↗

Glomerular lesions and the nephrotic syndrome in rabbits given saccharated iron oxide intravenously; with special reference to the part played by intracapillary precipitates in the pathogenesis of the lesions.

Intravascular precipitates, comprised at least in part of iron, formed regularly in rabbits given one or more injections of a saccharated iron oxide preparation intravenously, and these lodged in numerous capillaries throughout the body, particularly those of the lungs and kidneys. Large numbers of the brownish precipitates remained in the capillaries of the renal glomeruli during the first few days following injection of the iron, but most of them disappeared after 5 to 7 days, with only moderate amounts of brown pigment remaining in the endothelial cells of the renal glomeruli. Signs of acute injury of the glomerular tufts-namely) pyknosis of some of the endothelial cells, margination of leukocytes within the glomerular capillaries, and slight proliferation of the epithelial cells-also developed some 5 to 7 days following injection of the iron, along with marked proteinuria, which proved transitory if no further injections were given. When the iron preparation was given repeatedly over prolonged intervals, however, the proteinuria persisted and became extreme, and hypoproteinemia developed, often with hypercholesterolemia and transitory edema as well. Histological studies of the kidneys of rabbits manifesting the nephrotic syndrome, as just described, disclosed that virtually all the renal glomeruli were greatly altered, mainly owing to proliferation of the epithelial cells, together with some fibrosis and atrophy. Some of the rabbits having marked proteinuria and other functional changes eventually developed azotemia following repeated injections of the iron, and several of them lost weight and died; the renal glomeruli of these animals showed changes like those just described, but the alterations were more extensive. Considered together, the findings provide evidence that the intravascular precipitates first occluded the glomerular capillaries for a period of several days following injection of the iron and then largely disappeared from them just prior to the development of morphologic signs of glomerular injury and proteinuria. Hence the possibility was considered that the intracapillary precipitates might have produced acute injury to the walls of the glomerular capllaries through the agency of anoxia. But it is plain that the findings of the present study do not disclose the essential nature of the anatomical change responsible for the proteinuria, or the means whereby this was produced. The findings as a whole were briefly considered in relation to the pathogenesis of the nephrotic syndrome as it occurs naturally in human beings.

Animals↗