losartan-potassium and Polycystic-Kidney--Autosomal-Dominant

Erythropoietin (EPO) in the renal cortex is synthesized by fibroblast-like cells that are in direct contact with capillaries and adjacent tubular cells. Prompted by this anatomical relationship, we asked whether renal cells express EPO receptors (EPORs) through which EPO could act as a renotropic cytokine. We found that all regions of human, rat and mouse kidney, mesangial and proximal and distal tubular cells express authentic EPORs. Similar EPOR expression was detected in kidney cancer cells, and in cyst epithelia from polycystic kidneys. In vitro, EPO stimulated mitogenesis in all normal and malignant cells, and cell survival and motogenesis in injured tubular cells. Since the normal kidney is essentially unresponsive to EPO, we hypothesized that EPO's cytokine effects in the kidney are revealed when tubular cells are induced to proliferate by a prior insult, as occurs in acute renal failure. Accordingly, we found that EPO treatment of rats with 'ischemic' acute renal failure afforded renoprotection and accelerated functional recovery.

Topics: Acute Kidney Injury; Animals; Cytokines; Erythropoietin; Humans; Kidney; Kidney Neoplasms; Polycystic Kidney, Autosomal Dominant; Reference Values

Topics: Aged, 80 and over; Comorbidity; Drug Resistance; Erythropoiesis; Erythropoietin; Humans; Hydroxyurea; Janus Kinase 2; Male; Mutation, Missense; Phlebotomy; Point Mutation; Polycystic Kidney, Autosomal Dominant; Polycythemia; Polycythemia Vera; Ultrasonography

A small number of hemodialysis (HD) patients have normal hemoglobin (Hb) levels without the need for erythropoiesis-stimulating agents (ESAs). The factors associated with this condition have been little studied. The objective of this prospective study was to determine these factors in a prevalent population of HD patients.. All patients who had normal Hb levels and who had not received ESAs in the last 6 months (non-ESA group) were included. Epidemiological and laboratory data were collected and we performed an abdominal ultrasound to assess hepatic and renal cysts. This group was compared to a control group of 205 prevalent HD patients on ESA therapy (control group).. We included 45 patients (16% from the whole group) in the non-ESA group. In this group, there was a higher proportion of men (76.5 vs. 61%), patients were younger (61.1 ± 14.7 vs. 67.5 ± 15.2 years), had a longer duration of renal replacement therapy (RRT) (9.4 ± 8.3 vs. 5.3 ± 5.8 years) and had a higher prevalence of adult polycystic kidney disease (APKD) and hepatitis C virus (HCV) liver disease (42.2 vs. 10.2%), p < 0.01. In the non-ESA group, HCV+ patients had a lower prevalence of APKD (2.2 vs. 38.4%) and hepatic cysts (2.2 vs. 19.2%), but significantly higher endogenous erythropoietin levels (55.8 ± 37.1 vs. 30.9 ± 38.4 mU/ml). No significant differences in anemia, iron metabolism, insulin, IGF-1 and renin were found between non-ESA and control groups. Non-ESA patients had a significantly higher number of renal (90.6 vs. 36.5%) and hepatic cysts (12.5 vs. 3.4%), and these were also larger in size (3.3 ± 2.4 vs. 1.5 ± 0.8 cm). In the multivariate Cox analysis, independent predictor factors for absence of anemia in HD patients were number of renal cysts >10 cysts (95% CI 1.058-1.405; p = 0.00), HCV+ liver disease (95% CI 1.147-1.511; p = 0.05) and time on RRT (95% CI 1.002-1.121; p = 0.05).. The absence of anemia in HD patients is not infrequent. Its frequency is higher in men and younger patients with long-term RRT, in patients with HCV+ liver disease and in APKD. It is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Cysts; Erythropoietin; Female; Hematinics; Hepacivirus; Hepatitis C; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Polycystic Kidney, Autosomal Dominant; Prevalence; Prospective Studies; Renal Dialysis; Spleen; Ultrasonography

Topics: Anemia; Erythropoietin; Female; Hepatitis C; Humans; Kidney; Kidney Failure, Chronic; Male; Polycystic Kidney, Autosomal Dominant; Renal Dialysis

At the time of renal transplantation, erythropoiesis-stimulating agents and iron supplementation are routinely discontinued in the prospect of recovery of renal function. This recovery, however, is often delayed and suboptimal. In addition, blood loss because of frequent diagnostic phlebotomies may be substantial. Renal transplant recipients may thus be considered at high risk of anemia in the immediate post-transplant period. We performed a single-center observational study, including 391 recipients of a single kidney. Hemoglobin levels and parameters of iron metabolism were monitored during the immediate post-transplant period, i.e., the first 3 months after transplantation. Hemoglobin levels decreased by 3.8 ± 1.5 g/dl to reach a nadir of 9.1 ± 1.2 g/dl at day 7. Transient severe anemia was observed in 91.3% of the patients. Donor age, gender, renal diagnosis of polycystic disease, pretransplant hemoglobin and ferritin level, estimated glomerular filtration rate at month 3, and duration of initial hospitalization were observed to be independently associated with the hemoglobin level at month 3. Transient severe anemia is an almost universal observation in incident renal transplant recipients. Poor graft function, high donor age, and low iron stores are independently associated with low hemoglobin levels at month 3.

Topics: Adult; Aged; Anemia; Belgium; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Transplantation; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Prevalence; Risk Factors

Hepatitis C (HCV) infection is commonly seen in dialysis patients, but its long-term deleterious effects in these patients are unknown. We evaluated the effect of HCV infection on anemia in our hemodialysis population. This retrospective case control study was carried out from January 1999 to February 2007. The HCV positive patients were assessed for a 12-month period by quarterly lab results for the prevalence of anemia, iron stores, dialysis adequacy, and alanine aminotranferase levels. Their requirements of erythropoietin (EPO) and intravenous (IV) iron were assessed during these months of clinical stability. A control group of age-matched, race-matched, and gender-matched hemodialysis patients with no history of HCV was similarly assessed for anemia, iron stores, and EPO and IV-iron requirements. Twenty-two HCV-positive patients were included for comparison analysis with 44 control patients for 1:2 matching. The mean EPO requirement for the hepatitis group was 17,307 +/- 14,708 U/month in comparison with the control group, which required 49,134 +/- 49,375 U/month (p value <0.01). The mean dose of IV-iron was 120 +/- 143 mg/month for hepatitis patients and 163 +/- 112 mg/month in the control group (p=0.07). The patients with HCV have lower requirement of exogenous EPO replacement compared with their age-matched, gender-matched, and race-matched dialysis counterparts. The IV-iron requirement was not significantly different between the 2 groups but had a suggestive lower trend in the hepatitis group. This needs to be further studied in larger trials.

Topics: Adult; Aged; Anemia; Case-Control Studies; Cohort Studies; Erythropoietin; Female; Hepatitis C; Humans; Kidney Failure, Chronic; Male; Middle Aged; Patient Selection; Polycystic Kidney, Autosomal Dominant; Renal Dialysis; Retrospective Studies

Erythropoietin (EPO)-producing renal cell carcinomas (RCC) in patients with chronic renal failure secondary to autosomal dominant polycystic kidney disease (ADPKD) has not previously been reported. We report a case of EPO-producing RCC associated with ADPKD in a 66-year-old woman, and discuss the clinical and radiological findings.

Topics: Aged; Carcinoma, Renal Cell; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Kidney Neoplasms; Neoplasm Proteins; Polycystic Kidney, Autosomal Dominant

Topics: Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Polycystic Kidney, Autosomal Dominant; Renal Dialysis; Treatment Outcome

Topics: Adult; Erythrocyte Count; Erythropoiesis; Erythropoietin; Humans; Ketanserin; Kidney Failure, Chronic; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Renal Dialysis; Serotonin Antagonists

The Han:SPRD rat model for inherited polycystic kidney disease (PKD) was characterized (clinical parameters, morphology, immunohistochemistry and in situ hybridization). Homozygous animals died of uremia after three to four weeks with severe cystic transformation of virtually all nephrons and collecting ducts (serum urea: 616 +/- 195 mg/dl; kidney-to-body weight ratio: > 20%). In heterozygotes, slow progression of the disease led to death between the 12th and 21st month (median: 17 months; serum urea levels above 200 mg/dl). Kidney enlargement was moderate, and cysts were restricted to the cortex and outer medulla. Immunohistochemical markers showed that approximately 75% of the cysts were derived from the proximal tubule. Cystic transformation started in the proximal tubule with a sharp onset of basement membrane alteration and a loss of epithelial differentiation restricted to small focal areas. In these areas, alpha 1(IV) collagen and laminin B1 mRNA were enhanced as revealed by isotopic and non-isotopic in situ hybridization. Fibroblasts underlying the affected tubular portions were involved in matrix overexpression resulting in subepithelial accumulation of immunoreactive collagen IV and laminin. In later stages of cystic transformation distal nephron segments were affected as well. A reversal in epithelial polarity as judged from Na,K-ATPase-immunoreactivity was not observed. Renal immunoreactive renin-status was significantly decreased. Hematocrit was lowered in heterozygotes (40.4 +/- 5.8 vol% compared to 46.7 +/- 1.99 vol% in controls; P < 0.05) and total renal EPO mRNA was reduced to 36 +/- 14% of the mean value of control animals, whereas serum EPO levels were not significantly altered. We conclude that the Han:SPRD rat is a useful model for the study of human ADPKD since both diseases are similar in several aspects. The model is particularly suitable for the study of epithelial-mesenchymal interactions at the beginning of tubular cystic transformation.

Topics: Animals; Disease Models, Animal; Erythropoietin; Extracellular Matrix Proteins; Female; Hypertrophy; Kidney; Male; Mucoproteins; Polycystic Kidney, Autosomal Dominant; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Renin; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Uromodulin

Recombinant erythropoietin was used in the treatment of the anemic syndrome in 5 patients (4 women and 1 man), aged 45-63, with confirmed autosomal dominant polycystic kidney disease. All patients were with II stage chronic renal insufficiency. The treatment was conducted with Eprex (Silag, Switzerland) administered subcutaneously in a dose of 50 U/kg of body weight for three months. Once weekly, hemoglobin, hematocrit, erythrocytes, and serum iron were investigated in all patients. Simultaneously, we used recombinant erythropoietin in the same dose and treatment protocol on a control group of 3 women and 2 men with II stage chronic renal insufficiency but without polycystic kidney disease. The control patients were suffering from other diseases leading to uremia. In both groups, the hemoglobin and hematocrit were found to be significantly increased whereas their serum iron tended to decrease which required inclusion of iron containing preparations in the treatment. We found no significant differences both in the dynamics of influencing the disease and in the final results of the treatment with erythropoietin between the patients with polycystic kidney diseases and those without polycystosis and chronic renal insufficiency. No allergic reactions were observed during treatment. Arterial pressure was elevated in all patients. We think that recombinant erythropoietin can be used successfully in the treatment of renal anemia in patients with polycystic kidney disease and chronic renal insufficiency in the predialysis stage.

Topics: Anemia; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Recombinant Proteins