Decreased Urine Volume Research Articles

Comparison Between Lemonade and Potassium Citrate and Impact on Urine pH and 24-Hour Urine Parameters in Patients with Kidney Stone Formation

The past few decades have been notable for advances in minimally invasive techniques to treat kidney stones. Despite successful surgical management of calculi, the impact of diet on stone disease prevention remains an important factor. Dietary modifications can be applied to prevent stone recurrence in an economical manner that is acceptable to patients. Lemonade has been studied in the past and found to increase urinary citrate levels in small groups of patients. The present study examined the effect of lemonade intake on a change in urinary pH and improvement of urinary stone risk factors compared with potassium citrate treatment. A total of 21 stone-forming patients were treated with lemonade therapy and potassium citrate supplementation in a prospective cross-over trial. we performed 24-hour urine collections at baseline and with each treatment arm. the results between the two groups were examined to determine whether differences existed in the urinary stone risk factors. Potassium citrate, but not lemonade, improved citrate levels and urinary ph to a significant degree. patients taking potassium citrate had a significantly decreased urine volume compared with their urine volume drinking lemonade. neither lemonade nor potassium citrate affected the uric acid levels to a significant degree. The results of our study have shown that lemonade did not provide improvements in urinary citrate or pH levels but did assist patients in maintaining urine output compared with potassium citrate therapy.

A case of nephrogenic diabetes insipidus with a novel missense mutation in the AVPR2 gene

We describe a pediatric case of nephrogenic diabetes insipidus (NDI) with a novel missense mutation in the arginine vasopressin receptor 2 (AVPR2) gene. The patient, a 3-year-old boy, had polyuria (4357 ml/day, 7230 ml/m(2)/day) and polydipsia. Water deprivation testing demonstrated no decrease of urine volume, and urinary volume did not respond to subcutaneous injection of 0.1 U/kg pitressin. Molecular genetic analysis demonstrated that the patient had an AVPR2 missense mutation involving substitution of phenylalanine for tyrosine at position 205 (Y205F). It was also found that the patient's mother was heterozygous for this Y205F mutation. Analysis of the intermolecular interaction of the Tyr-205 hydrogen group by molecular modeling showed that Tyr-205 was located in transmembrane domain (TM) 5, and that its hydroxy group formed a hydrogen bond with Leu-169 main-chain =O located in TM 4. The mutation of Tyr-205 to phenylalanine would cause loss of this hydrogen bond and decrease or change the interaction between these TM coils, thus affecting the ability of AVP to bind to the receptor. According to this molecular model of AVPR2, the Y205F mutation would cause nephrogenic diabetes insipidus.

Erdheim-Chester disease: a rare cause of renal failure

A 52-year-old woman was admitted to our department because of renal failure. She had initially presented at the age of 50, with a thyroid mass requiring hemithyroidectomy. The histological diagnosis of the thyroid mass was that of a pseudo-inflammatory histiocitic tumour. For the next 2 years, the patient had no other problems. One week before admission, the patient noted vomiting and decreased urine volume. On admission, she had elevated blood pressure (180/80mmHg) and serum creatinine was 1060mmol/l (1 year previously, serum creatinine levels were normal). The patient had lower haemoglobin levels (9 g/dl) and hyperkalaemia (serum potassium of 7mmol/l). The rest of the serum biochemical analysis was in the normal range. In spite of a bladder catheter being placed, urine volume was minimal and a haemodialysis session was performed via a femoral catheter. A computed tomography scan (with intravenous medium contrast) was performed and showed bilateral compression of renal parenchyma by retroperitoneal mass (Figure 1). Left mass measured 8 9 13 cm and affected the right kidney, suprarenal gland and spleen. Right kidney showed diffuse infiltration and light hydronephrosis. A biopsy of retroperitoneal mass was performed. The left renal parenchyma was thinned and showed chronic hydronephrosis. Therefore, we decided to perform decompression of the right kidney. Left pyelography showed upper hydronephrosis and a nephrostomy was placed. The patient was free of symptoms and did not require dialysis after the procedure and her serum creatinine level stabilized at around 265mmol/l. Histological examination of the biopsy revealed an accumulation of foamy histiocytes in a background of fibrosis admixed with chronic inflammation (Figure 2). The histiocytic cell population was not immunoreactive for S100, CD21, CD23, CD34, ALK1 and LMP1. These histological findings were similar to the thyroid mass. On the basis of these findings, a diagnosis of Erdheim–Chester disease was made. No other lesions in eyes, long bones, lungs and heart were found in this patient.

Plasma concentration of antidiuretic hormone in response to intraruminal administration of butyrate in suckling calves

Our previous study has revealed that providing dry feeds increased the plasma concentration of antidiuretic hormone (ADH) in suckling calves, leading to altered water balance. To examine whether ketone bodies formed from ruminal fermentation-derived butyrate induced ADH secretion in suckling calves, the effects of intraruminal administration of butyrate on plasma concentration of ADH and ketone bodies, plasma and urine osmolality, and urine volume were examined. Six male Holstein calves aged 4 wk were used. Three levels of butyrate (0 g, 22 g and 44 g) were intraruminally administrated in a 3 × 3 Latin square design, and blood plasma and urine were analyzed. Plasma concentration of ketone bodies was increased by intraruminal administration of butyrate within 15 min in a dose-dependent manner, and the elevation of plasma levels continued until 4 h. Plasma concentration of ADH was also increased by the butyrate treatment, and it was higher in the 44 g butyrate group than in the 22 g butyrate group from 15 min to 2 h. The duration of the elevated plasma concentration of ADH was shorter than that of plasma concentration of ketone bodies. The relationship between plasma concentrations of ADH and those of ketone bodies was statistically significant, although the relationship was weaker. In accordance with the elevation of plasma ADH levels, the butyrate treatment resulted in the decreases in urine volume and increases in urine osmolality. Plasma osmolality was not different among the groups. The present results suggest that ruminal butyrate-derived ketone bodies are at least partly responsible for ADH secretion in suckling calves fed with dry feeds, and that the secreted ADH decreases urine volume through the increase in urine osmolality.

Acute Lethal Toxicity, Hyperkalemia Associated with Renal Injury and Hepatic Damage after Intravenous Administration of Cadmium Nitrate in Rats

Cadmium nitrate Cd(NO(3))(2) (CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD(50) of CdN was determined to be 5.5 mg/kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-beta-D-glucosaminidase/creatinine, beta(2)-microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN.

Urocortin 2 Infusion in Healthy Humans: Hemodynamic, Neurohormonal, and Renal Responses

We sought to examine the effects of urocortin (UCN) 2 infusion on hemodynamic status, cardiovascular hormones, and renal function in healthy humans. Urocortin 2 is a vasoactive and cardioprotective peptide belonging to the corticotrophin-releasing factor peptide family. Recent reports indicate the urocortins exert important effects beyond the hypothalamo-pituitary-adrenal axis upon cardiovascular and vasohumoral function in health and cardiac disease. We studied 8 healthy unmedicated men on 3 separate occasions 2 to 5 weeks apart. Subjects received placebo, 25-microg low-dose (LD), and 100-microg high-dose (HD) of UCN 2 intravenously over the course of 1 h in a single-blind, placebo-controlled, dose-escalation design. Noninvasive hemodynamic indexes, neurohormones, and renal function were measured. The administration of UCN 2 dose-dependently increased cardiac output (mean peak increments +/- SEM) (placebo 0.5 +/- 0.2 l/min; LD 2.1 +/- 0.6 l/min; HD 5.0 +/- 0.8 l/min; p < 0.001), heart rate (placebo 3.3 +/- 1.0 beats/min; LD 8.8 +/- 1.8 beats/min; HD 17.8 +/- 2.1 beats/min; p < 0.001), and left ventricular ejection fraction (placebo 0.6 +/- 1.4%; LD 6.6 +/- 1.5%; HD 14.1 +/- 0.8%; p < 0.001) while decreasing systemic vascular resistance (placebo -128 +/- 50 dynes x s/cm(5); LD -407 +/- 49 dynes x s/cm(5); HD -774 +/- 133 dynes.s/cm(5); p < 0.001). Activation of plasma renin activity (p = 0.002), angiotensin II (p = 0.001), and norepinephrine (p < 0.001) occurred only with the higher 100-mug dose. Subtle decreases in urine volume (p = 0.012) and natriuresis (p = 0.001) were observed. Brief intravenous infusions of UCN 2 in healthy humans induced pronounced dose-related increases in cardiac output, heart rate, and left ventricular ejection fraction while decreasing systemic vascular resistance. Subtle renal effects and activation of plasma renin, angiotensin II, and norepinephrine (at high-dose only) were observed. These findings warrant further investigation of the role of UCN 2 in circulatory regulation and its potential therapeutic application in heart disease.

Angiotensin‐(1–7) increases water intake and produces diuresis in association with down‐regulation of aquaporin‐1 during pregnancy in rats

Previous studies showed that kidney and urine levels of angiotensin-(1–7) [Ang-(1–7)] were increased in pregnancy (PR). Since the role of Ang-(1–7) on fluid and electrolyte homeostasis during PR has not been explored, we evaluated the effect of the Ang-(1–7) antagonist A-779 on kidney function. Virgin and PR rats at gestational day 7 and 11 received infusion of vehicle or Ang-(1–7) antagonist A-779 (48μg/kg/hr) for 8 days by osmotic minipumps. Metabolic studies were completed on treatment day 7–8. Virgin and PR at day 15 and 19 were sacrificed and kidneys were prepared for western blot analysis using polyclonal antibodies for AQP1 and AQP2. Urine volume increased progressively throughout gestation in vehicle, but not in A-779 treated rats. In 19d-PR rats, A-779 as compared to vehicle significantly decreased urine volume (19 ± 2 vs 28 ± 2 mL/24hr, p<0.05), increased urinary osmolality (1038 ± 80 vs 844 ± 66 mOsm/L, p<0.05), and decreased water intake (37 ± 3 vs 53 ± 3 ml/24hr, p<0.05), but had no effect on urinary sodium and potassium excretion. AQP1 kidney expression (28kDa) (15 ± 6 vs 4 ± 1 ROD, p<0.05) was significantly increased in A-779 treated 19d-PR rats without a change in AQ2 (29kDa). These studies suggest that Ang-(1–7) increases water intake and produces diuresis during late pregnancy by decreasing water reabsorption through down-regulation of the kidney AQP1 water channel. Sponsored by HL051952; AHA0615416

Effects of Saireito, a Japanese herbal medicine, on edema via antagonistic actions against aldosterone in anti-GBM nephritic rats

In order to clarify the diuretic mechanisms of Saireito, a Japanese herbal medicine, the mineralcorticoid receptor antagonistic action of Saireito was evaluated in anti-glomerular basement membrane (GBM) nephritic rats. Anti-GBM nephritis was induced in rats by the intravenous, injection of anti-GBM serum, and test drugs were administered 5 days after the induction of nephritis. In addition, we also investigated aldosterone-loaded mice to clarify the effects of test drugs on aldosterone signal transduction. In an in vitro study, a mineralocorticoid receptor binding assay of the components of Saireito was performed. Saireito and spironolactone inhibited the development of proteinuria and abdominal ascites in anti-GBM nephritic rats. Saireito and spironolactone increased the urine volume and decreased the abdominal saline content in aldosterone-loaded mice. Saikosaponin H, a component of Saireito, inhibited the receptor binding of aldosterone in the in vitro assay 50% inhibitory concentration ([IC(50)], 22 micromol/l). Saikosaponin H also inihibited the decrease in urine volume in aldosterone-loaded mice. These results suggest that the diuretic action of Saireito may be partly due to an antagonistic action on the mineralocorticoid receptor, exerted by saikosaponin H.

Ｍｅｔｈｏｔｒｅｘａｔｅ排せつ遅延に対し血液浄化法が有用だった１例―救援療法としての血液浄化法の評価―

The large dose administration of the carcinostatic agent methotrexate (MTX), a folic acid antagonist, is effective in treating osteosarcoma but its use is often accompanied by critical adverse effects. Forty-eight hours after administering MTX to a 9-year old female osteosarcoma patient the blood concentration of MTX was 283μM, approximately 280 times higher than the reference level, due to delayed excretion. However, the full amount of calcium folinate (Leucovorin® : LV) needed to antagonize such a high concentration of MTX in the blood was not available since it is produced in very small amounts. Therefore, we recommended blood purification methods such as hemodialysis plus hemoperfusion (HD+HP) and plasma exchange (PE) to reduce the high MTX concentration. HD+HP and PE achieved decreases in the MTX level of 76% and 34%, respectively. Though clinical tests implied hypofunction of the kidney and liver and myelosuppression, serious adverse effects such as decrease in urine volume, jaundice, and infection were not observed.Thus, the blood purification methods of HD+HP and PE were effective in emergency treatment for a patient with delayed excretion of MTX.

Anti-urolithiatic Effect of Petroleum Ether Extract Stem Bark of Crataeva adansonii. in Rats

Calcium oxalate nephrolithiasis in rats was induced by intraperitoneal injection of sodium oxalate (7 mg/100 g) daily for 7 days. A significant increase in the level of oxalate in urine and kidney with a decrease in urinary volume, pH, creatinine clearance, and lipid peroxide level was observed in animals receiving sodium oxalate as compared with saline-treated animals. Administration of petroleum ether extract (50 and 100 mg/kg, p.o.) of Crataeva adansonii. DC. along with sodium oxalate (prophylactically) and after 7 days of sodium oxalate injection (therapeutically) significantly decreased calcium oxalate content in urine and kidney and lipid peroxide level in liver and kidney compared with vehicle-treated group. Animals treated with petroleum ether extract (50 and 100 mg/kg, p.o.) of Crataeva adansonii. showed improved creatinine clearance as compared with vehicle group. Histological estimation of kidney treated with petroleum ether extract (50 and 100 mg/kg, p.o.) along with sodium oxalate strongly inhibited the growth of calculi and reduced the number of stones in kidney compared with group receiving vehicle. From this study, we conclude that both the prophylactic and therapeutic treatment with petroleum ether extract of bark of Crataeva adansonii. had an inhibitory effect on crystal growth, with improvement of kidney function as well as cytoprotective effect.

Delayed-Onset Neutropenia in a Patient Receiving Rituximab as Treatment for Refractory Kidney Transplantation

The use of rituximab against early refractory rejection in kidney transplantation or its preoperative administration for cross-match positive or ABO-incompatible transplants (1, 2, 3) has increased in the recent years, but caution is required regarding the occurrence of severe delayed-onset neutropenia. We describe a case of late-onset neutropenia secondary to rituximab administration. A 47-year-old woman with chronic nephritis (renal biopsy, mesangial proliferative glomerulonephritis) and a body weight of 45 kg started hemodialysis in August 2004. Blood tests for autoimmunity were negative for SLE. Then, a living-donor kidney was transplanted from her ABO-compatible sister on September 3, 2004. The preoperative cross-match and anti-HLA antibody were both negative, and FK, prednisolone, MMF, and basiliximab were used concomitantly. Early humoral rejection accompanied by decreased urine volume, edema and elevated creatinine was observed 48 hr later. Plasmapheresis was conducted in response 9 times on consecutive days, but because her condition was refractory and the risk of graft loss was imminent, rituximab at 150 mg/m2 was administered and resulted in a dramatic recovery. At her final visit on January 13, 2005, as an outpatient, her blood biochemical tests were normal with leukocyte count of 4260/μl, neutrophil count of 2340/μl, and platelet count of 27.6×104/ml, but 5 days later she was admitted into the hospital with sudden fever and diarrhea. The visceral function examination on admission was within the normal range, with leukocyte count of 1190/μl, agranulocytosis and visual determination was not possible. hypogammaglobulinemia, platelet count of 19.5×104/ml, and all viral and bacterial tests were negative. Bone mar-row biopsy revealed a condition of maturation arrest without hemophagocytosis, and the megakaryocytic series and erythrocytic series were within the normal range. With peripheral CD19 and CD20 both at 0%, the patient was placed in a clean room for supportive treatment, with consequent recovery from this neutropenia 7 days later. Six months after rituximab administration, CD19 and CD20 were both 0%, and in an examination after 8 months the values were still low with CD19 at 0.1% and CD20 at 0.5%. MMF administration was discontinued since the onset of neutropenia up till now to avoid over-immunosuppression. MMF immediately before onset was 0.5 g, and DLSTs on concomitant drugs were all negative. Since the transplant patients are not cancer patients, the absolute number of B-cells, which are the target of CD20, is much less than in the B-cell lymphoma patients, although the applied dose of rituximab for medical transplantation is 375 mg/m2 administered one to 4 times as with B-cell lymphoma. The occasional reports of severe delayed-onset neutropenia in the lymphoma patients who receive rituximab therapy (4–6) are also a cause for concern. The dose level of Rituximab to renal transplant patients was decided from the results of a phase I study on ML (7), pharmacokinetics of patients waiting for renal transplant (8). We urge the prompt establishment of methods for rituximab administration, and we also strongly warn that severe delayed-onset of neutropenia can occur even at small doses. Naoki Mitsuhata Ryuji Fujita Seiichi Ito Department of Urology Kure Kyosai Hospital Hiroshima, Japan Makoto Mannami Kojima Keimei Department of Urology Uwajima Tokushukai Hospital Uwajima, Japan

Nephrolithiasis complicating treatment of diabetes insipidus

A decrease in urine volume is considered the therapeutic goal of the treatment of central diabetes insipidus (DI) with desmopressin (dDAVP). A low urine volume is a risk factor for kidney stone formation. This is the first report of nephrolithiasis in association with DI. It is likely that successful therapy with dDAVP and the patient's own purposeful decreased fluid intake contributed to calcium oxalate stone formation. Prevention of stone recurrence requires an increase in urine volume. The patient's compliance with this recommendation led to an episode of acute hyponatremia, a well-known complication of dDAVP therapy. The challenge of the management of stones in the setting of DI requires balancing the conflicting goals of both decreasing and increasing urine volume.

EFFECTS OF SAW PALMETTO EXTRACT ON MICTURITION REFLEX OF RATS AND ITS AUTONOMIC RECEPTOR BINDING ACTIVITY

We examined the effects of saw palmetto extract (SPE) on the rat micturition reflex and on autonomic receptors in the lower urinary tract. The effect of SPE was examined on cystometrograms of anesthetized rats induced by intravesical infusion of saline or 0.1% acetic acid. SHR/NDmc-cp (cp/cp) rats received repeat oral administration of SPE and nighttime urodynamic function was determined. The autonomic receptor binding activity of SPE in the rat bladder and prostate was examined by radioligand binding assay. Intraduodenal administration of SPE (60 mg/kg) in anesthetized rat cystometry caused a significant increase in the micturition interval, micturition volume and bladder capacity during intravesical saline infusion. Also, similar administration of SPE at doses of 12 and 20 mg/kg significantly reversed the shortened micturition interval as well as the decreased micturition volume and bladder capacity due to 0.1% acetic acid infusion in a dose dependent manner. In conscious SHR/NDmc-cp (cp/cp) rats repeat oral administration of SPE (6 mg/kg daily) constantly increased the micturition interval and concomitantly decreased voiding frequency. SPE inhibited specific binding of [H]NMS ([N-methyl-H]scopolamine methyl chloride) (bladder) and [H]prazosin (prostate) with IC50 values of 46.1 and 183 microg/ml, respectively. SPE significantly alleviates urodynamic symptoms in hyperactive rat bladders by increasing bladder capacity and subsequently prolonging the micturition interval. Our data may support the clinical efficacy of SPE for the treatment of lower urinary tract symptoms.

Clinical Quiz

A 3.5-year-old boy was admitted because of fever and urinary symptoms. He was the first offspring of his healthy first-cousin parents, with a normal birth weight. After 2 months of breastfeeding, he was placed on formula milk. At 7 months of age, he had been admitted because of urinary-tract infection (UTI), failure to thrive (FTT), and steatorrhea. Radiological study showed a stone in his left kidney. His UTI was treated with antibiotics but his parents refused more studies. This time, he had steatorrhea and FTT (weight, height, and head circumference below the 5th percentile). In physical examinations, his heart and lungs were normal and there was no organomegaly or lymphadenopathy, but we did notice diminished deep-tendon reflexes. Further studies showed normal sweat test; urine white blood cells (WBC), 25 cells/high-power field; urine bacteria, >105/ml; serum WBC, 7200 cells/μl; Hg, 10.7 g/dl; prothrombin time (PT) activity, 84%; serum cholesterol, 28 mg/dl (45-82 mg/dl); triglyceride, 9 mg/dl (30-86 mg/dl); low-density lipoprotein, 16 mg/dl (60-140 mg/dl); high-density lipoprotein, 10 mg/dl (35-55 mg/dl). His parents lipoprotein profiles were normal. His peripheral blood smear and intestinal biopsy are shown in Figures 1 and 2. Meanwhile, his voiding cystouretherogram was normal and in radiologic study he had two stones in his left kidney. His UTI was treated with antibiotics and lithotripsy was done. The stone analysis showed a mixed stone of uric acid, calcium oxalate, and triple-phosphate.FIG. 1: Acanthocytes in peripheral blood smearFIG. 2: Lipid laden enterocytes in intestinal biopsyWhat is the diagnosis? A. Intestinal lymphangiectasia B. Cystic fibrosis C. Anderson's disease D. Abetalipoproteinemia E. Schwachman-Diamond syndrome F. Celiac disease ANSWER/DISCUSSION ANSWER: Abetalipoproteinemia (ABL). In fact, in lipoprotein electrophoresis there was an absence of apolipoprotein B. COMMENT: ABL is a rare autosomal recessive disorder caused by mutation in the gene of microsomal triglyceride transfer protein, which transfers lipids to apolipoprotein B (apoB). Abnormality in this protein will cause a virtual absence of apoB-containing lipoproteins [chylomicron, very-low-density lipoprotein (VLDL), (LDL)] and extremely low levels of triglyceride and cholesterol. Inability of intestinal enterocytes to secrete long-chain fatty acids into the blood will lead to an accumulation of lipids in the enterocytes (lipid-laden enterocytes), malabsorption of lipids and fat-soluble vitamins, steatorrhea, and FTT. In fact, most of the symptoms of ABL are due to vitamin deficiency, especially vitamin E. These findings are: bizarrely shaped red blood cells (acanthocytes) and mild anemia; neurologic problems starting with diminished deep-tendon reflexes, followed by gradual loss of distal lower-extremity vibratory and proprioception senses; dysmetria; ataxia, and spastic gait, and ophthalmologic problems (decreased night and color vision, progressive retinitis pigmentosa). Diagnosis is made by extremely low levels of cholesterol, triglyceride, VLDL, LDL, and apoB. Therapy includes avoidance of long-chain fatty acids and administration of fat-soluble vitamins. (1) On the other hand, hyperoxaluria and subsequent oxalate lithiasis can be due to increased oxalate production or absorption. Ca2+ in the intestinal lumen, by binding to oxalate and forming insoluble salts, decreases absorption of oxalate. In ABL (as in other fat-malabsorption disorders), excessive amounts of fat in the colon combine with Ca2+, leading to lower oxalate salt formation and increased oxalate absorption. This will lead to hyperoxaluria and oxalate stone formation. (2) Uric acid is responsible for formation of another type of kidney stone. The main determinant factor of uric acid supersaturation in the urine and subsequent stone formation is low urine pH. Decreased urine volume, high-purine diet, or increased endogenous uric acid production are other causes of uric acid stone formation. Unabsorbed dietary fatty acids in the intestinal lumen can cause an osmotic diarrhea and patients with chronic diarrhea are particularly at risk from uric acid stones, because they are often dehydrated, so they have a chronic metabolic acidosis and acidic urine. They also have lower urine volume. The dimensions of uric acid crystals closely match those of calcium oxalate and it has been suggested that the uric acid crystals promote heterogeneous nucleation of calcium. Finally, obstruction of urinary system by stones and subsequent stasis would be a risk factor for UTI and, in the presence of urea-splitting bacteria, urea and H+ could form triple-phosphate stones. (3) Two other inherited disorders that affect apoB-containing lipoproteins are Anderson's disease and familial hypobetalipoproteinemia. In Anderson's disease, only apoB48 is absent and acanthosytosis is rare. Familial hypobetalipoproteinemia is an autosomal co-dominant disorder. Patients with homozygous familial hypobetalipoproteinemia have exactly the same clinical picture as patients with ABL, but their parents, who are heterozygotes, have plasma concentrations of apoB and LDL that are one-quarter to one-half the normal levels.

Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice

The Tamm-Horsfall protein (THP; uromodulin), the dominant protein in normal urine, is produced exclusively in the thick ascending limb of Henle's loop. THP mutations are associated with disease; however, the physiological role of THP remains obscure. We generated THP gene-deficient mice (THP -/-) and compared them with wild-type (WT) mice. THP -/- mice displayed anatomically normal kidneys. Steady-state electrolyte handling was not different between strains. Creatinine clearance was 63% lower in THP -/- than in WT mice (P < 0.05). Sucrose loading induced no changes between strains. However, water deprivation for 24 h decreased urine volume from 58 +/- 9 to 28 +/- 4 microl x g body wt(-1) x 24 h(-1) in WT mice (P < 0.05), whereas in THP -/- mice this decrease was less pronounced (57 +/- 4 to 41 +/- 5 microl x g body wt(-1) x 24 h(-1); P < 0.05), revealing significant interstrain difference (P < 0.05). We further used RT-PCR, Northern and Western blotting, and histochemistry to study renal transporters, channels, and regulatory systems under steady-state conditions. We found that major distal transporters were upregulated in THP -/- mice, whereas juxtaglomerular immunoreactive cyclooxygenase-2 (COX-2) and renin mRNA expression were both decreased in THP -/- compared with WT mice. These observations suggest that THP influences transporters in Henle's loop. The decreased COX-2 and renin levels may be related to an altered tubular salt load at the macula densa, whereas the increased expression of distal transporters may reflect compensatory mechanisms. Our data raise the hypothesis that THP plays an important regulatory role in the kidney.

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na(+) concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na(+) transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and alpha-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of gamma-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na(+) transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.

Early start on continuous hemodialysis therapy improves survival rate in patients with acute renal failure following coronary bypass surgery

Acute renal failure requiring dialysis therapy after cardiac surgery occurs in 1% to 5% of patients; however, the optimal timing for initiation of dialysis therapy still remains undetermined. To assess the validity of early start of dialysis therapy, we studied the comparative survival between 14 patients who started to receive dialysis therapy when urine volume decreased to less than 30 mL/hr and another group of 14 patients who waited to begin dialysis therapy until the level of urine volume was less than 20 mL/hr for 14 days following coronary bypass graft surgery. Twelve of 14 patients who received early intervention survived. In contrast, only 2 of 14 patients in the late-dialysis group survived. There was a significant difference in survival between the two groups (p < 0.01). There were no significant differences between the two groups with respect to age, sex ratio, the APACHE (Acute Physiologic and Chronic Health Evaluation) II score, and the levels of serum creatinine at the start of dialysis therapy (2.9 +/- 0.2 mg/dL vs. 3.1 +/- 0.2 mg/dL), as well as the levels of serum creatinine at admission. We propose that the timing of the start for treatment of acute renal failure following cardiac surgery should be determined by the decrease of urine volume and not the levels of serum creatinine. Early start of dialysis therapy may help improve the survival of patients with acute renal failure following cardiac surgery.

A case of laryngeal posttransplantation lymphoproliferative disease

The development of posttransplant lymphoproliferative disease (PTLD) is strongly linked to infection with the Epstein-Barr virus (EBV), immunosuppression-state, the type of allograft, and EBV-seronegativity. A 18-month-old girl who had undergone living donor liver transplantation using the left lateral segment from her father was treated with tacrolimus and corticosteroid as an immunosuppressant regimen. She was readmitted 3 months after the transplant to evaluate the etiology of dyspnea and abdominal fullness as well as a decreased urine volume. She was diagnosed as an anastomotic stenosis of the hepatic vein for which she underwent balloon angioplasty. The treatment was repeated at postoperative month 5, 8, and 11. As postoperative 6 months, the result of the serological EBV-CA (IgG/IgM) was positive. In postoperative month 10, the EBV PCR serologic test become positive, and a laryngeal biopsy revealed PTLD. She was treated with acyclovir and gangyclovir as well as reduced immunosuppression. We report herein a rare case of laryngeal PTLD in a patient who had undergone living donor liver transplant with paternal allograft.

Outcomes associated with hypogonadism in women with chronic kidney disease

Outcomes associated with hypogonadism in women with chronic kidney disease

Antidiuretic Effects of a Novel Nonpeptide Vasopressin V2-Receptor Agonist, OPC-51803, Administered Orally to Dogs

We elucidated the pharmacological properties of a novel nonpeptide vasopressin V2-receptor agonist, OPC-51803 ((5R)-2-[1-(2-chloro-4-(1-pyrrolidinyl)benzoyl-2,3,4,5-tetra-hydro-1H-1-benzazepine-5-yl]-N-isopropylacetamide), via both in vitro binding experiments incorporating canine kidney and platelet membrane fractions and in vivo experiments that would determine the compound’s antidiuretic effects after oral administration to water-loaded dogs. OPC-51803 displaced [3H]arginine vasopressin (AVP) binding to canine V2 and V1a receptors, as determined by resulting Ki values of 15.2 ± 0.6 nM (n = 4) and 653 ± 146 nM (n = 4), respectively. These data indicate that OPC-51803 was about 43 times more selective for V2 receptors than for V1a receptors. Antidiuretic studies showed that orally administered doses of OPC-51803 (0.03 to 0.3 mg · kg−1) decreased urine volume and increased urinary osmolality in a dose-dependent manner in water-loaded dogs. Intravenous OPC-51803 infusions (0.3 and 3 μg · kg−1 · min−1) did not affect renal or systemic hemodynamics in anesthetized dogs. Since these results confirm that OPC-51803 shows antidiuretic action in dogs, the compound may be useful for treating AVP-deficient pathophysiological states.