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Renal AND Proteinuria [keywords]
- Lupus Nephritis in a Patient with Sickle Cell Disease. [JOURNAL ARTICLE]
- Case Rep Hematol 2013.:907950.
Introduction. The diagnosis of systemic lupus erythematosus (SLE) in patients with sickle cell disease (SCD) can be difficult to establish because the musculoskeletal, central nervous system, and renal manifestations are similar in both diseases. In the presented case, we highlight the diagnostic challenge that can evolve in patients with a concurrence of both diseases and we establish the importance of early recognition and treatment of lupus nephritis in patients with SCD. Case Presentation. We present a case of a 31-year-old African American female with sickle-C disease (hemoglobin SC) who was admitted to our hospital with complaints of periumbilical abdominal pain associated with intractable nausea and vomiting, abdominal distension, and worsening lower extremity edema. Urine studies revealed nephrotic range proteinuria and the immunological investigations were consistent with lupus. A renal biopsy revealed focal proliferative lupus nephritis. Conclusion. It is important to consider the presence of a coexisting autoimmune disease in a patient with sickle hemoglobinopathy who displays an atypical and multisystem presentation that is unresponsive to conventional therapies. When a significant kidney disease is present, a renal biopsy is critical in identifying the etiology of a renal abnormality in the setting of coexisting SLE and SCD.
- Low body weight in females is a risk factor for increased tenofovir exposure and drug-related adverse events. [Journal Article]
- PLoS One 2013; 8(12):e80242.
Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone diseases. Factors associated with these drug-related adverse events are poorly characterized. Our objective was to investigate such factors in patients treated long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with basal creatinine clearance >80 mL/min treated with tenofovir for at least 6 months and with at least one assessment of tenofovir plasma trough concentrations were considered. Tenofovir-associated adverse events were defined as the appearance of pathological proteinuria, worsening of renal function or bone demineralization. By multivariate regression analysis, we found that serum creatinine (p = 0.003) and body weight (p = 0.002) were the factors independently associated with plasma tenofovir concentrations. In particular, women with body weight<50 kg had significantly higher plasma tenofovir concentrations than those weighting >50 Kg (160±93 vs.71±52 ng/mL, p<0.001). High tenofovir plasma trough concentrations and the age of the patients were independently associated with the development of drug-related kidney and bone toxicity. In this retrospective study we have shown that HIV-infected women with low body weight are at risk to be exposed to high tenofovir plasma trough concentrations, ultimately resulting in a significant hazard to develop long-term tenofovir complications.
- Nephrotic syndrome associated with tyrosine kinase inhibitors for pediatric malignancy: case series and review of the literature. [JOURNAL ARTICLE]
- Pediatr Nephrol 2013 Dec 7.
Tyrosine kinase (TK) inhibitors are increasingly being used to treat a variety of pediatric malignancies. Reports in adult patients describe a range of effects of TK inhibitors on the kidney, including hypertension, proteinuria, acute kidney injury, and thrombotic microangiopathy (TMA); however, there are only a few reports of TK-inhibitor-associated nephrotic syndrome.We report four pediatric patients with various malignancies (chronic myelogenous leukemia, acute lymphoblastic leukemia, and glioma/renal cell carcinoma) who developed nephrotic syndrome during treatment with TK inhibitors (imatinib, sunitinib, dasatinib, and quizartinib). One of the four patients also had clinical features of TMA.Three of the four patients achieved complete remission of nephrotic syndrome with discontinuation of the TK inhibitor and have had no additional nephrotic syndrome relapses to date. The temporal relationship of nephrotic syndrome onset to TK-inhibitor therapy and resolution of nephrotic syndrome with cessation of therapy strongly imply an association in these patients.TK inhibitors are important therapies in pediatric cancer, and their use is expanding. Nephrotic syndrome with or without features of TMA is a potential complication of these therapies in children.
- Impact of angiotensin-converting enzyme gene polymorphism on proteinuria and arterial hypertension. [Journal Article]
- Coll Antropol 2013 Sep; 37(3):765-70.
Proteinuria is the hallmark of renal disease. In essential hypertension the onset of de novo proteinuria is associated with faster rate of progression of disease. Some authors have suggested that the DD genotype of the angiotensin-converting enzyme (ACE) gene would be an adverse renal prognosis factor. It may also have different effects on the reduction of proteinuria by ACE inhibitors in patients with proteinuria. Observations on the association between the ACE gene polymorphism and hypertension have been inconsistent, which might be due to ethnic and geographical variations. In this study was to investigated the relationship between ACE gene polymorphism and antiproteinuric effect of ACE inhibitors (ramipril) and to evaluate the possible association between I/D polymorphism and hypertension. We recruited 66 hypertensive patients (male 42, female 24) with overt proteinuria (urinary protein excretion over 500 mg/day). Patients were classified into three groups in accordance with ACE genotypes (17 DD; 35 ID; 14 II). They were treated with ramipril and prospectively followed up for one year. Various clinical parameters including age, body mass index (BMI), 24-h urine protein, creatinine, creatinine clearance (Ccr), systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP) were measured in the pre- and post-treatment periods. The ACE gene insertion/deletion(I/D) polymorphisms in intron 16 were determined by PCR. Results showed that there were no significant differences in the clinical parameters such as age, gender, serum creatinine, Ccr, SBP, DBP, MAP, and daily urinary excretion of protein among three groups (P > 0.05). ID genotype patients were found to have lower BMI (p = 0.031). ACE inhibition significantly reduced proteinuria in all genotype groups (p < 0.05). The percentage reductions of 24-h urinary excretion of protein were significantly different between the genotype groups (p = 0.042) and for DD genotype were significantly greater than in ID (79.2 +/- 28.9% vs 49.2 +/- 64.8%, P = 0.015). The slope of SBP was the main factor related to the slope of the percentage reduction of proteinuria, however, a significant negative correlation coefficient between these parameters was found (rs = -0.382, p = 0.002). We failed to find significant difference in outcomes of treatments with ACE inhibitor between male and female according the I/D polymorphism of the ACE gene. D allele in the ACE genotype could be a useful genetic marker with important clinical, therapeutic and prognostic implications in recognizing patients with proteinuria that are at greater risk of renal damage.
- 130 regulation of calcium transport channels in the duodenum, kidney, and placenta of a catechol-o-methyltranferase-inhibited mouse model. [Journal Article]
- Reprod Fertil Dev 2013 Dec; 26(1):178.
Preeclampsia is a pregnancy-specific disease characterised by concurrent development of hypertension, proteinuria, and oxidative stress in the placenta. Preeclampsia-like genetic models were also developed by modification of preeclampsia-related genes, such as catechol-O-methyltranferase (COMT). To investigate the pathophysiological conditions associated with preeclampsia, we divided pregnant mice into 4 groups (n=20): vehicle, COMT inhibitor, vehicle plus 2% supplemental calcium diet, and COMT inhibitor plus 2% supplemental calcium diet. The pregnancy mice were treated with the specific COMT inhibitor (ro41-0960, 2.5mgkg(-1)) from gestation Day 15 to 19. In parallel with treatment, the pregnant mice were fed with the 2% supplemental calcium diet or the normal diet for 5 days. All mice were sacrificed at 24h after last injection. Total RNA was extracted using Trizol regent according to the manufacturer's instructions. Using a quantitative reverse transcription-PCR (RT-qPCR), we measured the mRNA levels of several calcium transporters (TRPV5, TRPV6, PMCA1, and CaBP-9k) in the placenta, duodenum, and kidney. Placental TRPV5, TRPV6, and PMCA1 mRNA was significantly reduced by the COMT inhibitor, and the reduced PMCA1 mRNA was restored by calcium supplementation. Duodenal TRPV5, TRPV6, and PMCA1 mRNA was decreased in the COMT-inhibited mice, and slightly recovered after calcium supplementation. Although renal TRPV5, TRPV6, and PMCA1 mRNA was also decreased by COMT inhibition, their expression were regained by calcium supplementation compared with those of the control group. Taken together, these results indicate that physiological changes of the response to COMT inhibitor were similar to symptoms of preeclampsia, which may be related to disturbance of calcium metabolism during pregnancy. All statistical analyses were performed using Graphpad software (GraphPad, San Diego, CA, USA).
- Determinants of the creatinine clearance to glomerular filtration rate ratio in patients with chronic kidney disease: a cross-sectional study. [JOURNAL ARTICLE]
- BMC Nephrol 2013 Dec 5; 14(1):268.
Creatinine secretion, as quantified by the ratio of creatinine clearance (CrCl) to glomerular filtration rate (GFR), may introduce another source of error when using serum creatinine concentration to estimate GFR. Few studies have examined determinants of the CrCl/GFR ratio. We sought to study whether higher levels of albuminuria would be associated with higher, and being non-Hispanic black with lower, CrCl/GFR ratio.We did a cross-sectional analysis of 1342 patients with chronic kidney disease from the Chronic Renal Insufficiency Cohort (CRIC) who had baseline measure of iothalamate GFR (iGFR) and 24-hour urine collections. Our predictors included urine albumin as determined from 24-hour urine collections (categorized as: <30, 30-299, 300-2999 and >=3000 mg), and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic). Our outcome was CrCl/iGFR ratio, a measure of creatinine secretion.Mean iGFR was 48.0 +/- 19.9 mL/min/1.73 m2, median albuminuria was 84 mg per day, and 36.8% of the study participants were non-Hispanic black. Mean CrCl/iGFR ratio was 1.19 +/- 0.48. There was no association between the CrCl/iGFR ratio and urine albumin (coefficient 0.11 [95% CI-0.01-0.22] for higest verus lowest levels of albuminuria, p = 0.07). Also, there was no association between race/ethnicity and CrCl/iGFR ratio (coefficient for non-Hispanic blacks was-0.03 [95% CI-0.09-0.03] compared with whites, p = 0.38).Contrary to what had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than reported by several frequently cited reports in the literature.
- Age and gender differences in the relationship between hepatitis C infection and all stages of Chronic kidney disease. [JOURNAL ARTICLE]
- J Viral Hepat 2013 Dec 5.
Chronic kidney disease (CKD) is a worldwide health issue with heavy economic burden. Chronic hepatitis C virus (HCV) infection is a common cause of CKD, which can significantly impact the progression and mortality among patients with CKD. The prevalence of both illnesses is high in Taiwan. A multicentre and population-based cross-sectional study including 24 642 subjects was conducted to explore the association of HCV infection with the prevalence and severity of CKD. The measurements of metabolic parameters, eGFR and CKD stages were compared between subjects with HCV seropositivity and seronegativity. The analyses of association between HCV infection with CKD stages and evaluation of potential risk factors of CKD were performed by gender and age (≤ and >45 years). HCV-seropositive subjects accounted for 6.9% and had a significantly older age. The prevalence of CKD increased in those with HCV seropositivity (16.5%). Significantly higher prevalence of CKD stages ≥3 in HCV-seropositive subjects was noticed (7.8%). Age (>45 year), male gender, alcohol drinking, hypertension, creatinine and HCV infection were the significant factors associated with the presence of CKD. HCV seropositivity was an independent risk factor of developing CKD and associated with an increased risk of having CKD of all stages. The higher prevalence of earlier stage of CKD warrants longitudinal studies with frequent testing on renal function and sufficient duration to determine the changes of eGFR over time. Implementation of effective treatment intervention is also required for these subjects to prevent the progression of CKD to late stages.
- Outcome of tonsillectomy for recurrent IgA nephropathy after kidney transplantation. [Journal Article]
- Clin Transplant 2013 Nov.:22-8.
Since 2007, we have performed tonsillectomies for patients with recurrent immunoglobulin A nephropathy (IgAN) after kidney transplantation. Seven patients with primary IgAN showed biopsy-proven recurrent IgAN after living-donor kidney transplantation. They had persistent proteinuria or hematuria for an average of 40.3 months, and tonsillectomy was performed, on average, 75.6 months after kidney transplantation. In six patients with observation periods of more than one yr, good remission of urinary findings was observed after tonsillectomy. We classified the seven patients into three types of renal injury based on histological findings: severe, moderate, and mild. Two patients classified with severe renal injury at the time of tonsillectomy had other problems, such as refractory hypertension and bilateral sinusitis. They followed a rapidly progressive clinical course. One case already had moderate histological renal injury. He demonstrated prompt amelioration of urinary findings after tonsillectomy but immediate deviation from remission of proteinuria and hematuria. In the four cases presenting mild renal injury at tonsillectomy, the improved urinary findings and serum creatinine value after tonsillectomy have persisted. In conclusion, tonsillectomy may be a favorable treatment for cases of mild-grade IgAN. However, other treatments such as antihypertensive agents and diet therapy may be necessary in other grades.
- Proteinuria in paediatric patients with human immunodeficiency virus infection. [REVIEW]
- World J Clin Cases 2013 Apr 16; 1(1):13-18.
In human immunodeficiency virus (HIV)-infected people kidney disease is as an important cause of morbidity and mortality. Clinical features of kidney damage in HIV-infected patients range from asymptomatic microalbuminuria to nephrotic syndrome. The lack of specific clinical features despite the presence of heavy proteinuria may mask the renal involvement. Indeed, it is important in HIV patients to monitor renal function to early discover a possible kidney injury. After the introduction of antiretroviral therapy, mortality and morbidity associated to HIV-infection have shown a substantial reduction, although a variety of side effects for long-term use of highly active antiretroviral therapy, including renal toxicity, has emerged. Among more than 20 currently available antiretroviral agents, many of them can occasionally cause reversible or irreversible nephrotoxicity. At now, three antiretroviral agents, i.e., indinavir, atazanavir and tenofovir disoproxil fumarate have a well established association with direct nephrotoxicity. This review focuses on major causes of proteinuria and other pathological findings related to kidney disease in HIV-infected children and adolescents.
- Molecular profiling of acute and chronic rejections of renal allografts. [Journal Article]
- Clin Dev Immunol 2013.:509259.
Both antibody mediated (AMR) and T-cell mediated (TCMR) rejections either acute or chronic represent the main reason for late graft dysfunction. In this study we aimed to evaluate differences in the intrarenal expression patterns of immune system related genes in acute and chronic rejections. Graft biopsies were performed and evaluated according to Banff classification. Using the TaqMan Low Density Array, the intrarenal expressions of 376 genes relating to immune response (B-cell activation, T-cell activation, chemokines, growth factors, immune regulators, and apoptosis) were analyzed in the four rejection categories: chronic AMR, chronic TCMR, acute AMR, and acute TCMR. The set of genes significantly upregulated in acute TCMR as compared to acute AMR was identified, while no difference in gene expressions between chronic rejections groups was found. In comparison with functioning grafts, grafts that failed within the next 24 months after the chronic rejection morphological confirmation presented at biopsy already established severe graft injury (low eGFR, higher proteinuria), longer followup, higher expression of CDC20, CXCL6, DIABLO, GABRP, KIAA0101, ME2, MMP7, NFATC4, and TGFB3 mRNA, and lower expression of CCL19 and TRADD mRNA. In conclusion, both Banff 2007 chronic rejection categories did not differ in intrarenal expression of 376 selected genes associated with immune response.