Renal Risk Factors Research Articles

Caring for individuals with hypertension in CKD, especially those with low education

Hypertension remains prevalent worldwide. In this commentary, the need for more effective treatment of this cardiovascular and renal risk factor is discussed. We can treat hypertension more effectively by getting the blood pressure measurement right, understanding the link between albuminuria and hypertension, enabling the use of spironolactone to treat resistant hypertension through the use of drugs that bind potassium in the gut, and addressing the structural determinants of health.

C-reactive protein/albumin ratio is a predictive factor for prognosis in patients with metastatic renal cell carcinoma.

To evaluate the effect of pretreatment C-reactive protein/albumin ratio and modified Glasgow prognostic score on the prognosis in patients with metastatic renal cell carcinoma. A retrospective study was carried out in 176 patients with metastatic renal cell carcinoma who received first-line tyrosine kinase inhibitors. The effect of adding inflammatory prognostic scores to the International Metastatic Renal Cell Carcinoma Database Consortium model (International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio and International Metastatic Renal Cell Carcinoma Database Consortium-Glasgow prognostic score models) on overall survival was evaluated using receiver operating characteristic curves. The prognostic value of inflammatory prognostic scores (C-reactive protein/albumin ratio-modified Glasgow prognostic score) was tested using the Kaplan-Meier method and Cox proportional regression models. Patients were stratified into two groups using the cut-off value of 0.05: C-reactive protein/albumin ratio-low (<0.05) and C-reactive protein/albumin ratio-high (≥0.05). The area under the curve was significantly higher in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model (0.720) than that of the International Metastatic Renal Cell Carcinoma Database Consortium model (0.689) and the International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score model (0.703). Significant differences were observed in overall survival stratified by the number of risk factors in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio risk model between one or two and three or four factors (P<0.001), and three or four and five or more factors (P=0.001). For the patients in the International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk group, overall survival was significantly different between the C-reactive protein/albumin ratio-low and -high groups (P=0.001), whereas it was not significantly different between the patients with one and two International Metastatic Renal Cell Carcinoma Database Consortium risk factors (P=0.106). The C-reactive protein/albumin ratio is a simple and independent predictor of overall survival in patients with metastatic renal cell carcinoma. The predictive activity was significantly improved in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model compared with the International Metastatic Renal Cell Carcinoma Database Consortium/International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score models.

MON-287 CORRELATION OF HBA1c AND URINE ALBUMIN CREATININE RATIO (UACR) WITH RENAL AND CARDIOVASCULAR HEALTH RISK FACTORS IN PATIENTS WITH DIABETES MELLITUS

Renal and cardiovascular comorbidity are important risk factor for overall mortality in both Type 1 and 2 diabetes mellitus (DM) patients. Poor blood glucose control has an unfavourable impact on complications. It is also believed that development of kidney disease in these patients worsens cardiovascular risk. To better ameliorate these major vascular complications we have tried to study the correlation of HbA1c and UACR (two easily measured biomarkers) with modifiable clinical and biochemical parameters in DM patients. Both these biomarkers have the potential to facilitate prevention and management of several specific aspects of diabetes mellitus patients. A prospective observational cohort study was conducted between July 2015 and June 2018 in our clinic. All type 1 and 2 diabetes mellitus patients who consented to be part of this investigative trial were included. The presence of hypertension on clinical evaluation was noted. Conventional diabetes biomarkers (hemoglobin, HbA1c, serum creatinine / eGFR; serum lipid profile, serum albumin, urine albumin creatinine ratio.) were tested in the cohort.Correlation between HbA1c and UACR with clinical and laboratory biomarkers were studied. A total of 1077 patients were evaluated. There were 61% males. Of these 260 were of type 1 diabetes mellitus and 817 were type 2 DM patients .Hypertension (a major cardiovascular and renal risk factor) was significantly associated not only with high HbA1c and high UACR but also with renal functions (creatinine, eGFR) and poor glucose control in this cohort. Table 1. The biomarker HbA1c was significantly correlated positively with urine albumin creatinine ratio (nephropathy), serum total cholesterol (poor glycemic control).It was negatively correlated with serum albumin (nephropathy – albuminuria) and serum creatinine (preexisting impaired renal function, tight glycemic control and hypoglycemia).A high UACR was significantly (a) positively correlated with HbA1c (poor glycemic control), and (b) negatively correlated with hemoglobin (anemia of CKD). Table 2. Table 1Correlation of hypertension with biochemical factorsHypertensionHemoglobin (g/dl)HbA1c %Albumin g/dlUACR mcg/mgCreatinine mg/dleGFR ml/minHTN -12.99.73.8410.6121HTN+12.28.53.72671.555p value0.070.040.250.00000.00000.0000 Open table in a new tab Table 2Correlation between HbA1c and UACR with other biochemical parametersBiochemical ParameterHbA1c (%) R2 P valueUACR (mcg/mg) R2 P valueUACR mcg/mgR2 =+ 0.16P value= 0.0001-----------HbA1c (%)---------------R2=0.16P value =0.0001Hemoglobin (g/dl)R2= 0.07 P value =0.07R2= - 0.16P value 0.0001Serum Albumin (g/dl)R2= -0.13 P value =0.002R2= -0.26P value 2.2Creatinine (mg/dl)R2= -0.14 P value =0.001R2=0.23P value=4.2eGFR ml/min/1.73m2R2=0.26 P value = 9.6R2= -0.19P value =4.4Cholesterol (mg/dl)R2=0.13 P value = 0.004R2=0.03P value=0.48Triglycerides (mg/dl)R2=0.18 P value =2.9R2=0.04P value =0.26 Open table in a new tab Utilising easily available biomarkers(HbA1c and UACR) for risk prediction of cardiovascular and renal complications in DM patients may be a feasible approach in resource limited setting.

SAT-216 Renal risk for mortality after 15 years of follow up in a cohort of Toba aborigines in suburban Resistencia (Chaco, Argentina)

During 2003, 385 Toba aborigines were studied for cardiovascular disease (CVD) and renal risk factors. In 2018, after 15 years, 45 individuals died (11.7%). The causes were CVD 20 (45.5%) cancer 12 (27.3%) (n=), infectious (predominantly Tuberculosis) 9 (20.5%), 3 (6.6%) due to accidents and 1 (0.2%) missed. The objective is to compare risk factors in relationship to mortality in those who died vs alive ones. Medical records were revised. Weight, height, waist circumference (WC), urine and serum creatinine, fasting glucose, uPr/uCr ratio, GFR by MDRD-4 formula and renal risk (RR by KDIGO classification (no risk, moderate, high and very high risk); hypertension was defined as >140 mmHg systolic or > 90 mmHg diastolic blood pressure; diabetes as fasting glucose > 126 mg/dl. BMI was classified according to WHO as obesity (³ 30); central obesity for obesity was taken as WC >102 in men and >90 cm in women. Proteinuria was estimated (complexometric test) as uPr/uCr ratio mg/g: ≤150, stage 1, 150 ≤ 300 stage II and ≥ 300 stage III. Comparing cardiovascular and renal risk measured in 2003, between died Toba people 45 (11.7%) versus 313 (87.4%) alive ones, 27 (60%) and 167 (63%) (p=0,41) were females respectively . The first ones were older (53,87± 16,75 vs 33,54 ± 15,17 years old), had higher systolic BP, diastolic BP, WC, serum creatinine, serum glucose and lower GFR (statistical significance < 0, 01). Adjusting for age by multiple regression model remained still significative for groups: a) serum glucose (mg/dl) = 91+ 0.27 * year – 9.3 in alive ones; Urinary Creatinine (mg/dl): 116 – 0.401 * year * -15.6 in alive ones. HTA was present in 20 (44.5%) for died and 66 (21.1%) for alive ones, RR 2.99 (1.57-5.72) p=0.01; WC in 24 (53.3%) vs 99 (31.6%), RR 2.47 (1.31-4.64) p= 0.004; DBT 3 (6.7%) vs 4 (1.7%), RR 5.51 (1.19-25.51) p=0.04; Renal risk distribution was different between groups: very high risk in 6.7% vs 1.3%; high risk in 24.4% vs 10.2%; moderated in 17.8% vs 24.3%; and no CKD in 51.1% vs 64.2%, p= 0,03. In this cohort with high prevalence of CVD and renal risk, higher serum glucose and urine creatinine adjusted for age were associated with high risk for mortality . Probably CKD (estimated by MDRD formulae) did not reach statistical significance because the formulae corrects GFR by age. Renal risk distribution was a best predictor for mortality.

MON-257 Cardiovascular and renal risk progression after 15 years of follow up in a Toba aboriginal cohort (preliminary results)

Toba aborigines used to share a culture of hunters and gatherers; they got contact with civilization in the late nineteenth century, and, though many of them still live in rural areas, most have moved to suburban areas. During 2003, cardiovascular and renal risk factors (CVRRF) were studied in 385 Toba people living in suburban neighborhoods from Resistencia City (Chaco) one of the poorest regions of Argentina. In 2018, after 15 years, we began to re-study the same population, in order to evaluate mortality and progression of CVRRF. The objective now is to present preliminary results about progression of cardiovascular and renal risk in this suburban Toba cohort 65/340 of the surviving cohort were evaluated again, measuring weight, height, waist circumference (WC), creatinine, fasting glucose, and Proteinuria. CKD and renal risk was defined according to KDIGO Guidelines, GFR by MDRD-4 formula; hypertension as >140 mmHg systolic or ³90mmHg diastolic blood pressure (BP); Diabetes as fasting glucose ³126 mg/dl. Proteinuria as uPr/uCr ratio >150mg/g was considered positive. BMI was classified according to WHO as overweight (³25 and <30) and obesity (³30); Central obesity was defined as WC >102 cm in men and >90 cm in women. The analysis comparing baseline and current data was performed using Cox regression and hazard ratio Results: 65 Toba people, 42 (64.6%) females, mean age 49.3±13.5 years old have been re-evaluated so far. Statistical significance (p<0.05) in increasing quantitative variables were found in relation to: age (15.1±3.4), Systolic and Diastolic BP, WC, Weight, BMI, serum glucose, and MDRD. Negative significative differences were found in serum Creatinine (-0.1±0.009 mg/dl), urine Creatinine, and Protein excretion (-9.5 ± 8.5 mg/dl). Proportion of Toba Aborigines with Central Obesity, obesity, protein excretion taken as qualitative variables (yes/no) increased and are statically significative.(p=0,03). HR for proteinuria 5,20 (1,34-20,47).p=0,001 9 (15%) participants showed DBT now and CKD Renal Risk taken as qualitative variable increased significatively. Our preliminary results in part of the original cohort shows that surviving Toba people have increased weight, systolic and diastolic BP, BMI, and glycemia. Cardiovascular and renal risk increased. The increase in MDRD and reduction of urinary and serum creatinine could be interpreted as consequence of probably hyperfiltration associated to obesity, and the new diagnosed type 2 diabetes patients.

SAT-215 Mortality in an aboriginal Toba cohort after 15 years of follow-up in Resistencia City (Argentina)

Chaco province, Argentina, comprises a multiethnic population and is one of the poorest regions of Argentina. Almost 60.000 Toba aborigines, a gather and hunter culture, habits in it. They got contact with civilization in the late nineteenth century, and, though many of them still live in rural areas, most have moved to suburban areas. During 2003, cardiovascular and renal risk factors (CVRRF) were studied in 385 Toba people living in suburban neighborhoods from Resistencia City (Chaco) .

Human recombinant relaxin-2 does not attenuate hypertension or renal injury but exacerbates vascular dysfunction in a female mouse model of SLE

Systemic lupus erythematosus (SLE) is an autoimmune disease that disproportionately affects women of reproductive age and increases their risk for developing hypertension, vascular, and renal disease. Relaxin has potential beneficial therapeutic effects in cardiovascular disease through direct actions on the vasculature. The potential therapeutic benefit of relaxin on SLE-associated cardiovascular and renal risk factors like hypertension has not previously been tested. We hypothesized that relaxin would attenuate hypertension, renal injury, and vascular dysfunction in an established female mouse model of SLE (NZBWF1 mice). Serelaxin (human recombinant relaxin-2, 0.5 mg·kg-1·day-1) or vehicle was administered via osmotic mini-pump for 4 wk in female control (NZW) or SLE mice between 28 and 31 wk of age. Serelaxin treatment increased uterine weights in both groups, suggesting that the Serelaxin was bioactive. Mean arterial pressure, measured by carotid artery catheter, was significantly increased in vehicle-treated SLE mice compared with vehicle-treated controls, but was not changed by Serelaxin treatment. Albumin excretion rate, measured by ELISA, was similar between vehicle- and Serelaxin-treated SLE mice and between vehicle- and Serelaxin-treated control mice. Wire myography was performed using isolated carotid arteries to assess endothelial-independent and -dependent vasodilation, and data confirm that SLE mice have impaired endothelium-independent and -dependent relaxation compared with control mice. Serelaxin treatment did not affect endothelium-independent vasodilation, but exacerbated the endothelium-dependent dysfunction. These data suggest that, contrary to our hypothesis, Serelaxin infusion does not attenuate hypertension, renal injury, or vascular dysfunction in SLE, but worsens underlying vascular endothelial dysfunction in this experimental model of SLE. These data do not support the use of human recombinant relaxin-2 as an antihypertensive in the SLE patient population. NEW & NOTEWORTHY Relaxin is a peptide hormone commonly known for its role in pregnancy and for its use in recent clinical trials for the treatment of heart failure. Evidence suggests that relaxin has immunomodulatory effects; however, the potential therapeutic impact of relaxin in chronic immune mediated disease is unclear. This study tests whether recombinant human relaxin (Serelaxin) attenuates the progression of autoimmunity, and the associated cardiovascular consequences, in an experimental model of systemic lupus erythematosus.

CPS1 T1405N polymorphism, HDL cholesterol, homocysteine and renal function are risk factors of VPA induced hyperammonemia among epilepsy patients

PurposeValproic acid (VPA) is frequently used in the treatment of epilepsy. The adverse effects of VPA include hyperammonemia (HA) which is characterized by abnormally elevated blood ammonia level. Carbamoyl-Phosphate Synthase 1 (CPS1) is an enzyme catalyzing the initial step of removing ammonia from blood. Studies have demonstrated that the CPS1 polymorphism rs1047891-A allele carriers were susceptible to VPA-induced HA. However, the evidences remained controversial. In this study, we sought to validate the association between rs1047891 and VPA-induced HA by combining the association results from previous studies together. MethodsWe first conducted a systematic meta-analysis to determine whether rs1047891 was statistically significant. Then, we further evaluated the pleiotropic effects of rs1047891 using published genome-wide association studies (GWAS) and UKBB results. A conditional analysis was conducted to investigate whether the association between rs1047891 and VPA-induced HA was mediated by cardiovascular or renal disease risk factors or vice versa. ResultsThe allelic, dominant and recessive ORs of rs1047891-A were all significant in our fixed-effect meta-analysis. In GWAS catalog and UKBB data, rs1047891 was associated with basal metabolic rate, adiposity and hematology traits, cardiovascular and renal disease risk factors. We further proved that plasma HDL cholesterol and homocysteine level, in addition to eGFR by serum creatinine, were associated with VPA-induced HA risk independently from rs1047891 polymorphism. ConclusionIn conclusion, the SNP rs1047891 was associated with VPA-induce HA among epilepsy patients. Meanwhile, plasma HDL cholesterol and homocysteine level had independent effects from it.

Relationship Between PNPLA3 rs738409 Polymorphism and Decreased Kidney Function in Children With NAFLD.

Emerging evidence suggests that patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the major genetic variant associated with susceptibility to nonalcoholic fatty liver disease [NAFLD]) is associated with decreased kidney function in adults. Currently, it is uncertain whether this association also occurs in children/adolescents and whether any association is independent of liver disease severity. We enrolled a sample of 142 Caucasian children and adolescents with biopsy-proven NAFLD, presenting to the Liver Unit of the "Bambino Gesù" Children's Hospital. The glomerular filtration rate (e-GFR) was estimated using the Bedside Schwartz equation, whereas 24-hour proteinuria was measured using a radioimmunoassay method. Genotyping for the PNPLA3 rs738409 genotype was undertaken using the single-nucleotide polymorphism genotyping allelic discrimination method. Overall, 45 children had G/G, 56 had G/C, and 41 had C/C PNPLA3 rs738409 genotype, respectively. Children with G/G genotype had significantly lower e-GFR (107.5±20 versus 112.8±18 versus 125.3±23 mL/min/1.73 m2 , P=0.002) and higher 24-hour proteinuria (58.5±21 versus 53.9±22 versus 42.9±20 mg/day, P=0.012) compared with those with either G/C or C/C genotypes. After adjustment for age, sex, systolic blood pressure, measures of adiposity, homeostasis model assessment-estimated insulin resistance and biopsy-confirmed nonalcoholic steatohepatitis and stage of liver fibrosis, the presence of rs738409 G/G genotype was independently associated with both lower e-GFR (β coefficient: -23.6; 95% confidence interval [CI]: -36.3 to -10.8; P<0.001) and higher 24-hour proteinuria (β coefficient: 15.3; 95% CI: 1.12 to 30.5; P=0.046). Conclusion: Regardless of established renal risk factors and the histological severity of NAFLD, the PNPLA3 G/G genotype was strongly associated with decreasing kidney function and increasing 24-hour proteinuria in children/adolescents with histologically confirmed NAFLD.

Specific impact of past and new major cardiovascular events on acute kidney injury and end-stage renal disease risks in diabetes: a dynamic view.

BackgroundInterconnections between major cardiovascular events (MCVEs) and renal events are recognized in diabetes, however, the specific impact of atrial fibrillation (AF), heart failure (HF) and acute coronary syndrome (ACS) on the risk of end-stage renal disease (ESRD) on top of established renal risk factors is unclear in type 2 diabetes mellitus.MethodsWe conducted a retrospective study in 861 consecutive patients followed in a nephrology setting during the 2000–13 period.ResultsThe mean age was 70 ± 10 years, 65.1% were men and the estimated glomerular filtration rate (eGFR) was 42.4 ± 21.0 mL/min/1.73 m2. During follow-up (median 59 months), 194 patients reached ESRD. A history of AF, HF or ACS was associated with an increased risk of reduced baseline eGFR. In turn, reduced baseline eGFR resulted in a greater risk of new MCVE (especially HF) during follow-up. Finally, all new MCVEs were risk factors for subsequent acute kidney injury (AKI) {HF: hazard ratio [HR] 8.99 [95% confidence interval (CI) 7.06–11.4]; AF: HR 5.42 (3.91–7.52); ACS: HR 8.82 (6.24–12.5); all P < 0.0001} and ESRD [HF: HR 5.52 (95% CI 4.01–7.60), P < 0.0001; AF: HR 3.48 (2.30–5.21), P < 0.0001; ACS: HR 2.31 (1.43–3.73), P = 0.0006]. The AF- and HF-associated risks of ESRD were significant after adjustments on all renal risks of ESRD (gender, blood pressure, eGFR, albuminuria, renin–angiotensin blockers, retinopathy and AKI), but the association was less strong for ACS. Importantly, no association was noted between other major events such as stroke or infections and the risk of ESRD.ConclusionsPast and new cardiovascular events (more HF and AF than ACS) have a strong, independent impact on the development of ESRD above and beyond established risk factors in diabetes.

Recombinant Human Relaxin‐2 Treatment in an Experimental Female Mouse Model of Autoimmune Disease with Hypertension

Relaxin is a peptide hormone commonly known for its role during pregnancy; however, it has been postulated to have beneficial therapeutic effects in cardiovascular disease through direct actions on the vasculature. Systemic lupus erythematosus (SLE) is an autoimmune disease that, for reasons that are not completely understood, disproportionately affects women of reproductive age and increases their risk for developing hypertension, cardiovascular and renal disease. The potential therapeutic benefit of relaxin on SLE associated cardiovascular and renal risk factors like hypertension has not previously been tested. The objective of this study was to test the efficacy of relaxin to attenuate hypertension, renal injury, and vascular dysfunction in an established female mouse model of SLE (NZBWF1 mice). To test this, Serelaxin (human recombinant relaxin‐2, 0.5 mg/kg/day) or vehicle (saline) was administered via osmotic mini‐pump (Alzet 1002) for 4 weeks in NZW (Control) or SLE mice between 28 and 31 weeks of age. Mean arterial pressure was measured by carotid artery catheters in conscious mice at the conclusion of the study. Urinary albumin excretion, a marker of renal injury, was determined at the conclusion of the study by albumin ELISA in overnight samples collected in metabolic cages. Wire myography was performed using isolated carotid arteries to assess endothelial‐independent and –dependent vasodilation in response to increasing concentrations of sodium nitroprusside and acetylcholine, respectively (10−8–10−4 M). Serelaxin‐treated control and SLE mice had significantly increased uterine weights (p&lt;0.05) compared to vehicle‐treated mice, suggesting that the Serelaxin was bioactive. Mean arterial pressure was significantly increased in vehicle‐treated SLE mice compared to vehicle treated controls (134 ± 5 mmHg vs. 111 ± 3, n=9–12, p&lt;0.05). Blood pressure was not changed in Serelaxin‐treated SLE (139 ± 5 mmHg, n=12) or control mice (115 ± 3 mmHg, n=10). Albumin excretion rate was similar between vehicle‐(23.6 ± 17.5 mg/day, n =11) and Serelaxin‐treated (35.7 ± 16.1 mg/day, n= 11) SLE mice, and between vehicle (1.1 ± 0.9 mg/day, n=15) and Serelaxin‐treated (0.1 ± 0.1 mg/day, n=13) control mice. Wire myography data confirm previously published studies showing that SLE mice have impaired endothelial‐independent (Figure 1) and ‐dependent (Figure 2) relaxation compared to control mice. Serelaxin treatment did not affect endothelial‐independent vasodilation, but appears to have exacerbated the endothelial‐dependent dysfunction. These data suggest that, contrary to our hypothesis, Serelaxin infusion does not attenuate hypertension, renal injury, or vascular dysfunction in SLE under these experimental conditions. In fact, Serelaxin, through its direct actions on the vasculature, may worsen the underlying vascular endothelial dysfunction in this experimental model of SLE.Support or Funding InformationVA Merit Award (BX002604‐01A2), AHA 18PRE34020108, NIH (P01HL051971, P20GM104357, U54GM115428, R01HL134711, T32HL105324‐05)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study.

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12-1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29-3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07-1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06-1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01-19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41-24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

Complications and Risks of Percutaneous Renal Biopsy.

BACKGROUND:Renal biopsy performed in native and transplant kidneys is generally considered a safe procedure.AIM:In this study, we evaluated renal biopsy complications and risk factors in one nephrology facility.MATERIAL AND METHODS:We conducted a three-year retrospective study on patients who underwent renal biopsy between January 2014 and December 2016. Strict written biopsy protocol was followed. Clinical and laboratory data were obtained from medical charts. Complications were categorised as minor and major, according to the need for intervention. Minor complications included macrohematuria and/or hematoma that did not require intervention. Major complications included hematuria or hematoma with fall of hematocrit that required a blood transfusion, surgery or caused death. A binary logistic regression model was used to analyse the possible factors associated with complications after the biopsy.RESULTS:We analysed 345 biopsies; samples were taken from patients aged from 15-81 years, of whom 61% were men. A total of 21 (6%) patients developed a complication, 4.4% minor and 1.7% major complications. There were no nephrectomy or death due to biopsy intervention. Overweight patients, as well as those with higher creatinine, lower hemoglobin, higher blood pressure and biopsy due to AKI had higher chances to develop complications (p = 0.037, p = 0.023, p = 0.032, p = 0.002, p = 0.002, respectively). The patients’ age, gender, kidney dimension, number of passes and uninterrupted aspirin therapy were not found as significant predictors of complications. In the multivariate logistic model, body weight (OR = 1.031, 95%CI = 1.002-1.062), lower hemoglobin (OR = 0.973, 95%CI = 0.951–0.996) and hypertension (OR = 1.025, 95%CI = 1.007-1.044) increased the risk of complications in biopsied patients.CONCLUSION:Renal biopsy is a safe procedure with a low risk of complications when strict biopsy protocol is observed. Correction of anaemia and blood pressure is to be considered before the biopsy.

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Essential hypertension is a clinical diagnosis based on the presence of an elevated systemic blood pressure on physical examination without a clear inciting cause. It has multiple etiologies and is not a homogeneous disorder. Hypertension contributes to the development and progression of atherosclerotic cardiovascular diseases, and antihypertensive treatment reduces the risk of fatal and nonfatal myocardial infarction, stroke, and congestive heart failure. Although hypertension is frequently present in nondiabetic individuals with low levels of proteinuria and chronic kidney disease, reducing blood pressures in this population does not reliably slow nephropathy progression. Many of these patients with recent African ancestry have the primary kidney disease "solidified glomerulosclerosis" that is strongly associated with renal-risk variants in the apolipoprotein L1 gene (APOL1). This kidney disease contributes to secondarily elevated blood pressures. The APOL1-associated spectrum of nondiabetic nephropathy also includes proteinuric kidney diseases, idiopathic focal segmental glomerulosclerosis, collapsing glomerulopathy, severe lupus nephritis, and sickle cell nephropathy. This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension. Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se.

Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial

BackgroundAcute heart failure (HF) patients with renal insufficiency and risk factors for diuretic resistance may be most likely to derive incremental improvement in congestion with the addition of spironolactone. MethodsThe Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) trial randomized 360 acute HF patients with reduced or preserved ejection fraction to spironolactone 100 mg daily or usual care for 96 hours. The current analysis assessed the effects of study therapy within tertiles of baseline estimated glomerular filtration rate (eGFR) and subgroups at heightened risk for diuretic resistance. ResultsAcross eGFR tertiles, there was no incremental benefit of high-dose spironolactone on any efficacy endpoint, including changes in log N-terminal pro-B-type natriuretic peptide and signs and symptoms of congestion (all P for interaction ≥ 0.06). High-dose spironolactone had no significant effect on N-terminal pro-B-type natriuretic peptide reduction regardless of blood pressure, diabetes mellitus status, and loop diuretic dose (all P for interaction ≥ 0.38). In-hospital changes in serum potassium and creatinine were similar between treatment groups for all GFR tertiles (all P for interaction ≥ 0.18). Rates of inpatient worsening HF, 30-day worsening HF, and 60-day all-cause mortality were numerically higher among patients with lower baseline eGFR, but relative effects of study treatment did not differ with renal function (all P for interaction ≥ 0.27). ConclusionsHigh-dose spironolactone did not improve congestion over usual care among patients with acute HF, irrespective of renal function and risk factors for diuretic resistance. In-hospital initiation or continuation of spironolactone was safe during the inpatient stay, even when administered at high doses to patients with moderate renal dysfunction.

Reduced Kidney Function in Tenofovir Disoproxil Fumarate Based Regimen and Associated Factors: A Hospital Based Prospective Observational Study in Ethiopian Patients.

Purpose Tenofovir disoproxil fumarate (TDF), a drug broadly used in combination antiretroviral therapy, is associated with renal dysfunction but the prevalence varied from country to country and it is not known in Ethiopia. The objectives of this study were to assess the prevalence of renal dysfunction and risk factors associated with it and the mean change in estimated glomerular filtration rate in human immunodeficiency virus infected patients receiving TDF based antiretroviral regimen at Tikur Anbessa Specialized Hospital. Method It was a hospital based prospective cohort study. The study participants were treatment naïve HIV infected patients initiating TDF containing combination antiretroviral therapy or switched to it because of adverse events. Multivariable logistic analysis was used to identify variables which have significant association. Result A total of 63 study participants were studied, 16 (25.4%) of whom had fall in eGFR greater than 25% relative to baseline. Only age greater than 50 years, baseline CD4 count less than 200 cells/mm3, and baseline proteinuria were significantly associated with renal dysfunction in multivariable logistic regression. There was -8.4 ml/min/1.73m2 mean change in estimated glomerular filtration rate relative to baseline at six months of study. Conclusion The renal dysfunction (defined as decline in eGFR greater than 25%) was found in a quarter of the study population. The long term impact and the clinical implication of it are not clear. Future prospective study is required with large sample size and long duration to ascertain the prevalence of decline greater than 25% in estimated glomerular filtration rate and its progression to chronic kidney disease.

Adult Cord Blood Transplantation (CBT) Recipients Have a High Incidence of Early Acute Kidney Injury (AKI) and AKI Increases Long-Term Chronic Kidney Disease (CKD) Risk

Introduction While adult double unit CBT (dCBT) has disease-free survival comparable to that of HLA-matched adult donor allografts, frequent patient (pt) comorbidities combined with chemotherapy/TBI & cyclosporine-A (CSA) contribute to AKI risk. Using KDIGO criteria, we analyzed renal injury incidence & risk factors in adults undergoing dCBT. Methods Adult dCBT pts transplanted 2006-2016 for hematologic malignancies using Cy/ Flu/ Thio/ TBI 400 cGy & CSA (therapeutic range 250-450)/ MMF were analyzed. Using day 0 - 100 creatinines, maximum grade (gr.) AKI [gr. 1 (1.5 - 3-fold baseline)] was calculated. If pts had multiple episodes, the highest grade was analyzed. The 2-yr CKD incidence (> 90 days of GFR Results 153 pts [median 51 years (range 23-65), 114/153 (75%) acute leukemia, 27/153 (18%) African, 88/153 (58%) CMV seropositive] were transplanted. No patient had chronic kidney disease pre-dCBT; 32/153 (21%) had hypertension & 12/153 (8%) were diabetic. Median aaHCT-CI was 3 (range 0-9) with 92/153 (60%) pts having a score > 3. 34 (22%) pts had High-Very High rDRI diagnoses. Median pre-dCBT albumin was 4 (range 2.6 - 5.2). 96% of pts engrafted, 76% had grade II-IV acute GVHD by day 100 & 90% were alive & disease-free at day 100 (11 TRM, 3 relapse). 127 pts had AKI (45 gr. 1, 60 gr. 2, & 22 gr. 3) for a day 100 grade 1-3 AKI cumulative incidence of 83% (95%CI: 77-89) (median onset 40 days, range 0-96) & 54% (95%CI: 46-62) for gr. 2-3 AKI (median onset 43 days, range 0-96) (Figure 1). The mean of the 3-day mean CSA level preceding AKI onset was high at 360 ng/ml. African ancestry, CMV seropositivity & low day -7 albumin level & post-dCBT variables of ICU admission, nephrotoxic drug exposure & bacteremia were associated with gr. 1-3 AKI (Table 1A). In multivariate analysis, low day -7 albumin, ICU admission & nephrotoxic drugs were significant (Table 1B). With a median 40 months (range 12-125) survivor follow-up, 34/109 (31%) evaluable pts had CKD at 2-yrs with 1 pt requiring long-term dialysis. Grade 2-3 AKI prior to day 100 was associated with a higher likelihood of having CKD at 2-yrs: 38% vs 25% (Figure 2). Conclusion dCBT recipients are at significant risk for AKI which increases the likelihood of long-term CKD. Early recognition of impending AKI & prompt intervention is critical to mitigate severe kidney injury & long-term impairment. Prevention strategies include adequate hydration, tight CSA level control & substitution of non-nephrotoxic medications (e.g. Letermovir CMV prophylaxis instead of pre-emptive foscarnet, non-aminoglycosides antibiotics, azoles rather than amphotericin, PO cidofovir instead of IV). Investigation of novel GVHD prophylaxis that could permit lower CSA dosing & early AKI detection using biomarkers should also be investigated.

Renal function and risk factors for renal disease for patients receiving HIV pre-exposure prophylaxis at an inner metropolitan health service.

BackgroundPre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) significantly reduces the risk of HIV acquisition. TDF is a known nephrotoxin however, renal dysfunction from TDF is mostly reversible following discontinuation.AimsTo describe the renal function, risk factors for renal disease and associated clinical testing practices in a cohort of PrEP patients.MethodsA retrospective review was conducted of all PrEP patients commenced on TDF/FTC at an inner metropolitan sexual health clinic in Sydney, Australia between April 2016 and July 2017, with follow-up data obtained at 3-monthly intervals until 18 months.Results525 patients met inclusion criteria. Patients were almost exclusively male and median age was 34 years (IQR: 28 to 42). At baseline, 1.5% had an estimated glomerular filtration rate (eGFR) <70 mL/min/1.73m2. A small significant drop in eGFR of -2.5 mL/min/1.73m2 (p<0.05) occurred between PrEP commencement and the first follow-up period, followed by a progressive decline in eGFR of -0.38 mL/min/1.73m2 per month (95%CI: -0.57 to -0.20; p<0.001). Renal impairment (eGFR <70 mL/min/1.73m2) occurred in 6.5% of patients and persisted across consecutive follow-up periods in five (1.0%) patients. Patients aged ≥40 years had a greater risk of renal impairment than younger patients (HR 3.9, 95%CI: 1.8 to 8.4; p<0.001), despite similar rates of eGFR decline (p = 0.19). PrEP was discontinued in two patients (0.4%) due to renal function concerns.ConclusionPrEP use led to an initial drop in eGFR and a more gradual progressive decline subsequently, but significant renal impairment remained uncommon up to 18 months of follow-up.

Factors Associated with Asymptomatic Proteinuria in Adult Nigerians. A Community-Based Study

Introduction: Early detection of proteinuria is early detection is a cost-effective method of assessing individuals with and without risk factors for chronic renal disease. Proteinuria is common in adults and may present a clinical challenge in the absence of obvious renal disease or risk factors especially in the tropics. Few studies in Nigeria have assessed the prevalence of proteinuria in adults using the dipstick method. The aim of this study was to document the prevalence of proteinuria among residents of a community in Enugu, south east Nigeria. Methods: This was a cross-sectional descriptive study carried out in an isolated urban slum settlement in Enugu, south east Nigeria. Dipstick testing of freshly voided early morning mid-stream urine samples was done to detect proteinuria. For database management and statistical analyses, SPSS version 23 was used. Results: A total of 262 individuals were recruited for the study, 165 (63%) females and 97 (37%) males. The participants’ age ranged from 18 to 90 years, averaging 43.7 ± 15.5. Trace amounts of protein were detected in urine samples of 225 (85.9%) individuals. Significant proteinuria was detected in 3.8% of the participants and was significantly higher 40 - 49-year-olds (6%). p = 0.02 and 0.02 respectively. Significant correlates of proteinuria were lower diastolic blood pressure and current tobacco use. Lower body mass index weakly correlated with proteinuria. Conclusion: The prevalence of significant early morning proteinuria in a community-based study in Enugu was 3.8%. Significant correlates of proteinuria included low diastolic blood pressure and tobacco use. Community based awareness programs targeted at prevention of chronic renal diseases should be incorporated in public health programs.

Study of the effect of different iron-chelating agents on early renal glomerular and tubular function markers in children with beta-thalassemia

Background Advances in the management of patients of beta-thalassemia major (BTM) and the advent of effective chelators have led to the discovery of many renal complications. Mechanisms of renal impairment in BTM are still not fully investigated. Chronic anemia and hypoxia, iron overload and its complications, and direct nephrotoxic effects of some chelators are the commonly used explanations. Objectives In this cross-sectional study, the aim was to investigate the prevalence of renal impairment in patients with BTM using some of both conventional and early markers of glomerular and tubular renal function and to investigate the relation between them and iron overload (s. ferritin) and the use of a specific chelator. Patients and methods The study included 60 transfusion-dependent patients with BTM without overt renal disease or risk factors, for example, diabetes mellitus, and 30 age-matched and sex-matched healthy children as a control group (group C). Patients were divided into two equal groups according to type of chelator: group A children receiving standard deferoxamine (DFO) and/or deferiprone and group B children receiving deferasirox (new treatment). Serum levels of ferritin, creatinine, and blood urea nitrogen; albumin/creatinine ratio (ACR) in urine; estimated glomerular filtration rate using Schwartz formula; urinary beta 2 microglobulin (UB2MG); and urinary calcium/creatinine ratio were measured in all patients and healthy control children. Results Serum creatinine was within the normal range in most of the patients, and no significant differences were found between the two thalassemic groups and the control group (P=0.473). ACR in urine and UB2MG were significantly higher in the two thalassemic groups, and the deferasirox group showed significantly higher levels than both DFO and/or deferiprone group and control group (P1=0.05 and P2=0.005, respectively, for ACR and P1=0.025 and P2=0.000, respectively, for UB2MG). UB2MG was abnormally high in 67 and 76% of the DFO and/or deferiprone group and deferasirox group, respectively, followed by microalbuminuria (16 and 30%, respectively). Glomerular hyperfiltration was prevalent, but there were no significant differences in the median of the three groups (P=0.766). Hypercalciuria was also prevalent in the two thalassemic groups with abnormally elevated urinary calcium/creatinine ratio in 30% of both groups but without significant differences in the median of the three groups (P=0.123). Serum ferritin was significantly positively correlated with ACR (P=0.002) and with UB2MG (P=0.000). Conclusions ACR can be used as an early marker of glomerular function. Deferasirox use is probably safe in the usual doses in low-risk patients, keeping into consideration that high doses of deferasirox cause disruption of the renal function.