Diabetes mellitus as a cause or comorbidity of chronic kidney disease and its outcomes: the Gonryo study

Background

Diabetes mellitus (DM) is a major cause of end-stage kidney disease (ESKD). However, the difference in renal outcomes between DM patients with non-diabetic renal disease (DM and NDRD) and those with diabetic nephropathy (DN) is controversial. The aim of the present study was to evaluate the differences among patients with DN, DM, and NDRD, and non-DM chronic kidney disease (CKD) in a prospective observational study.

Methods

We extracted the data of 2484 patients from 11 nephrology care centers and categorized into three groups as described above. The primary outcome was ESKD requiring renal replacement therapy.

Results

During the median follow-up of 4.44 years, 281 patients (11.3%) developed ESKD. Renal outcomes of DM and NDRD patients were similar to those of non-DM patients (p ≥ 0.05). At CKD stage G3b, the hazard ratios (95% confidence intervals) of ESKD were 7.10 (2.46–20.49) in DN patients and 0.89 (0.19–4.24) in DM and NDRD. The annual change in the estimated glomerular filtration rate (eGFR) in DN patients was significantly larger than that in other groups at stage G3b (?9.7%/year).

Conclusions

We found that DN patients have a higher risk for ESKD than DM and NDRD or non-DM patients. In particular, GFR rapidly declined in DN at stage G3b. DM and NDRD patients can accomplish equally beneficial renal outcomes as non-DM CKD, regardless of their similar metabolic profiles as DN. In conclusion, we should prudentially consider the risk stratification of DM whether cause or comorbidity of CKD.

     

Rationale and study design of a randomized controlled trial to assess the effects of maintaining hemoglobin levels using darbepoetin alfa on prevention of development of end-stage kidney disease in non-diabetic CKD patients (PREDICT Trial)

Background

Anemia associated with high mortality is a common complication of chronic kidney disease (CKD). Target hemoglobin (Hb) levels for CKD treatment remain controversial: Recent guidelines recommend a maximum of 13 g/dL to avoid increased risk of CVD. However, some smaller studies show slower progression of renal function loss with high Hb targets. Recently, darbepoetin alfa targeting Hb 11–13 g/dL was reported to improve renal composite outcome of Japanese patients compared with a low Hb group maintained at 9.0–11.0 g/dL using epoetin alfa (HR 0.66; 95 % CI 0.47–0.93). The high Hb group showed significant reduction of left ventricular mass index and improved quality of life. Sub-analysis revealed greater beneficial effects in non-diabetic stage 5 CKD patients. This randomized controlled trial, PREDICT, aims to confirm the impact of targeting Hb levels of 11–13 g/dL using darbepoetin alfa with reference to a low Hb target of 9–11 g/dL.

Methods

We calculated the number of subjects (N = 440) necessary to detect a statistically significant level of α = 0.05 (two-sided) and statistical power of 80 % for a minimum follow-up period of 2 years on the basis of a previous study.

Results

The study enrolled 498 non-diabetic Japanese patients with eGFR 8–20 mL/min/1.73 m². The primary outcome is a composite renal endpoint (starting chronic dialysis, transplantation, eGFR 6 mL/min/1.73 m² or less, 50 % decrease in eGFR). Average follow-up period is 2 years and the study ends in 2016.

Conclusion

PREDICT will determine the optimum target Hb for Japanese patients with non-diabetic CKD.(ClinicalTrials.gov No. NCT01581073).

     

Impact of Delta Hemoglobin on Provider Transfusion Practices and Post-operative Morbidity Among Patients Undergoing Liver and Pancreatic Surgery

Background

Delta hemoglobin (ΔHb) is defined as the difference between the preoperative Hb and the lowest post-operative Hb level. We sought to define the impact of ΔHb relative to nadir Hb levels on the likelihood of transfusion, as well as characterize the impact of ΔHb and nadir Hb on morbidity among a large cohort of patients undergoing complex hepatopancreatobiliary (HPB) surgery.

Methods

Patients who underwent pancreatic or hepatic resection between January 1, 2009 and June 30, 2015 at Johns Hopkins Hospital were identified. Data on the perioperative ΔHb, nadir Hb, as well as blood utilization were obtained and analyzed. Multivariable logistic regression models were used to identify the factors associated with ΔHb and the impact of ΔHb on perioperative morbidity. A Bayesian model was used to evaluate the correlation of ΔHb and nadir Hb with the likelihood of transfusion, as well as the impact on morbidity.

Results

A total of 4363 patients who underwent hepatobiliary (n?=?2200, 50.4 %) or pancreatic (n?=?2163, 49.6 %) surgery were identified. More than one quarter of patients received at least one unit of packed red blood cells (PRBC) (n?=?1187, 27.2 %). The median nadir Hb was 9.2 (IQR 7.9–10.5)?g/dL resulting in an average ΔHb of 3.4 mg/dL (IQR 2.2–4.7) corresponding to 26.3 %. Both ΔHb and nadir Hb strongly influenced provider behavior with regards to use of transfusion. Among patients with the same nadir Hb, ΔHb was strongly associated with use of transfusion; among patients who had a nadir Hb ≤6 g/dL, the use of transfusion was only 17.9 % when the ΔHb?=?10 % versus 49.1 and 80.9 % when the ΔHb was 30 or 50 %, respectively. Perioperative complications occurred in 584 patients (13.4 %) and were more common among patients with a higher value of ΔHb, as well as patients who received PRBC (both P?<?0.001).

Conclusions

The combination of the Hb trigger with ΔHb was associated with transfusion practices among providers. Larger ΔHb values, as well as receipt of transfusion, were strongly associated with risk of perioperative complication following HPB surgery.

     

Effects of topiroxostat in hyperuricemic patients with chronic kidney disease

Background

Hyperuricemia is associated with chronic kidney disease (CKD). Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has a strong effect against hyperuricemia, limited data are available on its renoprotective effect against CKD.

Methods

This study was conducted between October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered 40 mg/day of topiroxostat twice daily. All patients were followed for a year. To elucidate the effects of topiroxostat, we evaluated the clinically documented primary indication of progression, viz. laboratory evidence of kidney function decline (reference indicator), uric acid, and hypertension in different patient groups, separated according to their baseline uProt levels and baseline eGFR.

Results

Topiroxostat treatment resulted in significant reduction in SUA (?1.53 mg/dL), systolic blood pressure (?8.9 mmHg), diastolic blood pressure (?5.0 mmHg), and urinary protein excretion (?795.5 mg/gCr) compared with baseline values. However, serum creatinine and urinary NAG levels, and estimated glomerular filtration rate did not change significantly.

Conclusions

Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect in hyperuricemic patients with CKD. Further studies are required to clarify whether topiroxostat prevents the progression of renal disease and improves the prognosis of CKD patients.

     

Effect of daprodustat on anemia in patients with chronic kidney disease: a meta-analysis

Background

The efficacy of daprodustat for the treatment of anemic patients with chronic kidney disease (CKD) remains controversial. The aim of the study is to perform a meta-analysis of randomized controlled trials to evaluate the efficacy and safety of daprodustat for anemic patients with chronic kidney disease.

Methods

We searched Medline, Embase, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries for randomized controlled trials comparing daprodustat with placebo for anemic patients with CKD.

Results

Four studies were included. Compared with placebo groups, daprodustat groups significantly increased hemoglobin (WMD 1.29 g/dL; 95% CI 0.96–1.62, p?<?0.00001), transferrin (WMD 0.67 g/dL; 95% CI 0.45–0.89, p?<?0.00001), and total iron binding capacity (WMD 9.97 g/dL; 95% CI 6.07–13.8, p?<?0.00001). Daprodustat groups significantly decreased hepcidin (WMD ??76.1 μg/L; 95% CI ??91.8 to ??60.3, p?<?0.00001) and ferritin (WMD ??63.6 μg/L; 95% CI ??96.6 to ??30.7, p?=?0.0002) compared with that of placebo groups. In addition, there was no significant difference in adverse events between the two groups.

Conclusion

Daprodustat could improve hemoglobin without increasing adverse events in the short term. Daprodustat may be another valuable choice for anemic patients with chronic kidney disease in the future.

     

Low 1,25-dihydroxyvitamin D level is associated with erythropoietin deficiency and endogenous erythropoietin resistance in patients with chronic kidney disease

Purpose

Erythropoietin (EPO) deficiency and resistance to endogenous EPO is an important pathophysiological feature in anemia of chronic kidney disease (CKD). Low 1,25 dihydroxyvitamin D [1,25(OH)₂D] level is known to contribute to anemia of CKD. We aimed to investigate the associations between serum 1,25(OH)₂D and anemia, EPO deficiency, and endogenous EPO resistance in patients with CKD.

Methods

This study included 409 patients with CKD [glomerular filtration rate (GFR)?<?60 ml/min/1.73 m²] who were not on dialysis therapy. Patients on exogenous EPO therapy and patients with iron deficiencies were excluded. Endogenous EPO resistance was assessed by calculating the ratio of endogenous EPO to hemoglobin (Hb) (endogenous EPO/Hb ratio). The associations of Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio with clinical and laboratory variables were investigated by univariate and multivariate analyses.

Results

In univariate analysis, serum 1,25(OH)₂D level was correlated with the Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio. Multiple regression analysis revealed that the serum 1,25(OH)₂D level remained significantly associated with the Hb level (β?=?0.532, P?<?0.001), endogenous EPO level (β?=?0.149, P?=?0.010), and the endogenous EPO/Hb ratio (β?=???0.187, P?=?0.002), even after adjusting for other confounding factors, including the levels of parathyroid hormone and the inflammatory marker C-reactive protein.

Conclusion

The serum 1,25(OH)₂D level exhibited significant associations with anemia, EPO deficiency, and endogenous EPO resistance in CKD patients. These associations were independent of secondary hyperparathyroidism and inflammation status.

     

Safety and usage of darbepoetin alfa in children with chronic kidney disease: prospective registry study

Background

Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD).

Methods

In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded.

Results

A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5 %) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0 %), gastroenteritis (6.0 %), and hypertension (4.1 %). Six patients (1.9 %) died (unrelated to DA). Four patients (1.3 %) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4–2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2–11.7 g/dl, respectively. Overall, 48 patients (15.0 %) received ≥1 transfusion.

Conclusions

No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients.

     

A nationwide prospective cohort study of patients with advanced chronic kidney disease in Japan: The Reach-J CKD cohort study

Background

Epidemiology and outcomes of Japanese patients with advanced chronic kidney disease (CKD)—an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m²—has remained largely unexamined.

Methods

We conducted a nationwide survey to determine the distribution of Japanese CKD patients, and are conducting a cohort study of these patients. A questionnaire eliciting details about facilities and their CKD practices was sent to all clinics/hospitals with nephrologists. Based on the survey results, we recruited 2400 advanced CKD patients receiving nephrologist care from at least 30 representative facilities throughout Japan, selected randomly with stratification by region and facility size. Through patient questionnaires and nephrologist-practice surveys aligned with the international CKD Outcomes and Practice Patterns Study (CKDopps), we shall annually or semi-annually collect patient, physician and clinic data prospectively, detailing CKD practices for 5 years, with a primary outcome of death or renal replacement therapy initiation, and secondary outcomes being decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular event.

Results

Of 790 eligible, responding facilities, 330 (41.8%) treat ≥80 advanced CKD patients in the average 3-month period. Regional distribution of these facilities is similar to that of persons in the general population. Hence, the 30 facilities selected for data collection appear to be geographically representative in Japan.

Conclusions

Our study will enhance understanding of various CKD practices and biological data associated with CKD progression, and allow international comparisons using the CKDopps platform. This will provide evidences to improve the health and quality of life for patients with advanced CKD.

     

Anemia as a risk factor for all-cause mortality: obscure synergic effect of chronic kidney disease

Background

Anemia is common in chronic kidney disease (CKD) and may be associated with mortality in CKD patients. However, few studies have examined this relationship in Asian populations.

Methods

A total of 62,931 Japanese people (age 64.0 ± 8.0 years; men 38.5%) were followed up from 2008 to 2012. Participants were divided into six groups in accordance with their estimated glomerular filtration rate (eGFR) (<45, 45–59, ≥60 mL/min/1.73 m²) and by hemoglobin levels (13.0 g/dL for men; 12.0 g/dL for women). Hazard ratio and confidence interval (CI) for mortality with a combination of eGFR and anemia were calculated. After matching using propensity score (PS) for anemia, survival analysis between anemic and non-anemic people, independent from some variables, including eGFR, was performed.

Results

A total of 828 (1.3%) participants died (non-anemic vs. anemic, 1.2 vs. 2.3%, p < 0.01). Multivariable Cox analysis showed that, independent of eGFR levels, anemic people had significantly higher mortality. Anemic people were found to have significantly poorer survival than non-anemic people as per a log-rank test (p < 0.01) for the PS-matching cohort. Further stratified logistic analysis using PS in the overall cohort odds ratio (95% CI) showed 2.25 (1.89–2.67) with p < 0.01.

Conclusion

The results of the present study showed that anemia was an independent risk factor of all-cause mortality.

     

Prevalence of acute kidney injury during pediatric admissions for acute chest syndrome

Background

Patients with sickle cell disease are at risk for developing chronic kidney disease (CKD). Acute kidney injury (AKI) has been linked to progression to CKD, but limited data exist to determine its role in acute complications of sickle cell disease. We hypothesized that AKI occurs in pediatric patients admitted for acute chest syndrome (ACS) and prolongs hospitalization.

Methods

We conducted a 6-year retrospective review of pediatric patients with ACS admitted to a single medical institution.

Results

Of the 149 pediatric patients admitted for ACS during the 6-year study period, 12 (8 %) developed AKI. Comparison of patients with and without AKI revealed a significant association between AKI and a larger drop in hemoglobin value from baseline (2.7 vs. 1.4 g/dL; p?=?0.003), a lower hemoglobin value at admission (6.4 vs. 7.5 g/dL; p?=?0.03), and an increased white blood cell count at admission (33.1 vs. 19.8?×?10⁹/L; p?<?0.0001), respectively. AKI (p?<?0.0001) together with need for advanced respiratory support (biphasic positive airway pressure or mechanical ventilation) (p?<?0.0001) and need for exchange transfusion (p?<?0.0001) were associated with prolonged hospitalization.

Conclusions

Clinicians should monitor pediatric patients hospitalized for ACS for the development of AKI as a potentially modifiable risk factor for prolonged hospitalization.

     

Short- and long-term outcomes after non-severe acute kidney injury

Background

Severe acute kidney injury (AKI) is associated with chronic kidney disease (CKD), cardiovascular events and increased mortality. However, little is known about the prognosis in hospitalized population suffering from non-severe AKI episodes. The aim of this study is to determine the impact of non-severe AKI episodes in cardiovascular events, mortality and CKD, on short and long term.

Methods

Retrospective cohort study to 360 patients who met the criteria for diagnosis of AKI according ADQI guidelines with full recovery of renal function after the AKI episode, admitted between January 2000 and December 2010 in our hospital. Follow-up was 4 years after the diagnosis of AKI. Covariates included demographic variables, baseline creatinine and diagnosis of comorbidities.

Results

360 AKI survivor patients were included. Twenty five of them (6.7%) had developed CKD after 1-year follow-up. Hypertension (OR 1.62; 95% CI 1.2–2.6, p < 0.05) and serum creatinine >2.6 mg/dL in AKI (OR 1.7; 95% CI 1.2–3.7, p < 0.05) were independent risk factors. After 4-year follow-up, 40 patients (18.3%) had developed CKD; age >66 years was an independent risk factor (OR 1.03, 95% CI 1.03–1.06, p < 0.05). Mortality rate at 4 years was 25.3% and was significantly higher in CKD patients (OR 4.3, 95% CI 1.13–4.90, p < 0.05) and patients >66 years (OR 1.12, 95% CI 1.02–1.06, p < 0.05). The incidence of cardiovascular events also was higher in CKD patients than in non-CKD patients (62.7 vs. 21.7%, p < 0.05).

Conclusion

Even after fully recovered non-severe AKI episodes, some patients develop CKD and those have an increase in the incidence of cardiovascular events and long-term mortality.

     

Effect of combined vitamin D receptor activator and lanthanum carbonate on serum fibroblast growth factor 23 level in predialysis patients (CVD-LAF study): design and method

Background

Whether vitamin D receptor activator (VDRA) use is beneficial in chronic kidney disease (CKD) is unclear, because it is possible that VDRA increases serum fibroblast growth factor 23 (FGF23) levels. We will conduct a randomized controlled trial in predialysis patients to determine the effect of VDRA alone or in combination with lanthanum carbonate (LC) on serum FGF23 levels.

Methods

This is a single-center, open-label, randomized controlled trial. Enrollment will commence February 1, 2018, using the following inclusion criteria: (1) age?≥?20 years, (2) CKD with an estimated glomerular filtration rate of 10–45 mL/min/1.73 m², (3) serum adjusted calcium level?<?9.5 mg/dL, (4) serum phosphate level 4.0–6.0 mg/dL, and (5) serum intact parathyroid hormone (PTH) level?≥?60 pg/mL. Study patients will be randomized 1:1 to receive alfacalcidol alone or in combination with LC. The initial dose of alfacalcidol will be 0.25–0.5 µg once a day according to serum adjusted calcium level. The initial dose of LC will be 250 mg once a day. We will measure serum intact and C-terminal FGF23 at 0, 4, 8, 12, 24, and 52 weeks. The primary outcome will be serum FGF23 level at 24 weeks compared with baseline.

Discussion

This study aims to determine whether low-dose oral VDRA increases serum FGF23 level and whether the combination of VDRA and LC inhibits this increase. The results will be useful in the management of CKD–mineral and bone disorder in predialysis patients.

Trial registration

UMIN000030503. Registered 20 January 2018.

     

Necessity for autologous blood storage and transfusion in patients undergoing pancreatoduodenectomy

Purpose

To establish which patients undergoing pancreaticoduodenectomy (PD) need autologous blood storage and transfusion.

Methods

Autologous blood was collected and stored for 69 patients scheduled to undergo PD, and not used in 50 patients. Based on the use of the deposited autologous blood and the estimated postoperative hemoglobin (Hb) level when blood was not deposited, we divided the patients into a “transfusion necessary” group and a “transfusion unnecessary” group. By comparing the two groups, we proposed a method of scoring to predict the necessity for storing autologous blood.

Results

The “transfusion necessary” group comprised 6 patients (2 who received homologous blood transfusion and 4 with an estimated postoperative Hb of <8.0 g/dL) and the “transfusion unnecessary” group comprised 63 patients (24 whose autologous blood was discarded and 39 with an estimated Hb ≥8.0 g/dL). By analyzing the differences between the groups, including the preoperative hemoglobin level and the need for portal vein resection, we devised a scoring system to predict the necessity of collecting autologous blood. The scoring significantly correlated with the proportion of patients who did not require autologous blood storage and transfusion.

Conclusions

Not all patients benefited from autologous blood storage and transfusion. Our scoring system proved useful for identifying which patients required autologous blood storage and transfusion during PD.

     

The impact of serum uric acid reduction on renal function and blood pressure in chronic kidney disease patients with hyperuricemia

Background

Febuxostat is tolerable in chronic kidney disease (CKD) patients with hyperuricemia. However, the long-term effect of lowering uric acid with febuxostat on renal function and blood pressure has not been elucidated.

Methods

This was a 2 years retrospective observational study. 86 CKD patients with hyperuricemia who continued with allopurinol (allopurinol group, n?=?30), switched from allopurinol to febuxostat (switched group, n?=?25), or were newly prescribed febuxostat (febuxostat group, n?=?31) were included in this study. Serum uric acid, estimated glomerular filtration rate (eGFR), blood pressure, and urinary protein were analyzed. Moreover, the impact of serum uric acid reduction on renal function and blood pressure was assessed.

Results

Serum uric acid in the switched and febuxostat groups was significantly reduced at 6 months (switched group; 8.49?±?1.32–7.19?±?1.14 mg/dL, p?<?0.0001, febuxostat group; 9.43?±?1.63–6.31?±?0.90 mg/dL, p?<?0.0001). In the allopurinol group, serum uric acid was increased (6.86?±?0.87–7.10?±?0.85 mg/dL, p?=?0.0213). eGFR was significantly increased (35.2?±?12.8–37.3?±?13.9 mL/min/1.73 m², p?=?0.0232), while mean arterial pressure (93.1?±?10.8–88.2?±?9.5 mmHg, p?=?0.0039) was significantly decreased at 6 months in the febuxostat group, resulting in the retention of eGFR for 2 years.

Conclusions

The impact of serum uric acid reduction might have beneficial effects on CKD progression and blood pressure. However, a large prospective study is needed to determine the long-term efficacy of febuxostat therapy in CKD patients with hyperuricemia.

     

Low white blood cell count is independently associated with chronic kidney disease progression in the elderly: the CKD-ROUTE study

Background

Elevated white blood cell (WBC) count is a well-known predictor of chronic kidney disease (CKD) progression. However, elderly patients commonly fail to develop a high WBC count in response to several diseased states and may instead present a low WBC count. Therefore, we hypothesized that low WBC count, in addition to high WBC count, is associated with CKD progression in the elderly.

Methods

We conducted a prospective cohort study using 3-year follow-up data from the CKD Research of Outcomes in Treatment and Epidemiology study. In the present study, participants aged over 60 years with pre-dialysis CKD stages G2–G5 were eligible. Patients were stratified into three groups according to WBC count using tertiles (T). The primary outcome was a composite of end-stage renal disease and a 50% reduction in estimated glomerular filtration rate. Data were analyzed using Cox proportional hazard models with adjustments for covariates.

Results

We enrolled 697 patients (males, 69%). The median WBC count was 6100 cells/µl (T1, <5400, n = ?222; T2, 5400–6900, n = ?235; T3, ≥6900, n = 240). During a median follow-up of 868 days, the primary outcome was observed in 170 patients, whereas 54 patients died. T1 and T3 had significantly higher hazard ratios (HR) than T2 (T1, HR 1.69, 95% confidence interval 1.14–2.51; T3, HR 1.63, 95% confidence interval 1.10–2.41). Moreover, T1 had a significantly higher adjusted HR (1.54, 95% confidence interval 1.00–2.37).

Conclusion

Low WBC count is independently associated with CKD progression in the elderly.

     

Serum endocan and circadian heart rate variability in non-dialysis stage 5 chronic kidney disease patients

Background

Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that elevated heart rate (HR) is a risk factor for cardiovascular mortality. We investigated the link between serum endocan and circadian heart rate variability in non-dialysis stage 5 CKD patients.

Methods

In a cross-sectional study, we enrolled 54 prevalent n non-dialysis stage 5 CKD patients (32 males, aged 48.2?±?14.92 years). HR was measured with an automatic system. Serum endocan level was analyzed by ELISA.

Results

Night/day HR ratio was independently predicted by serum endocan level (P?<?0.01) and hypertension history (P?<?0.05). Adjusted R² of the model was 0.222.

Conclusion

Increased serum endocan is significantly associated with circadian heart rate variability in non-dialysis stage 5 CKD patients. Further investigation is needed to explore the potential benefits of serum endocan lowering therapy in this patient group.

     

Impact of low-density lipoprotein cholesterol on decline in estimated glomerular filtration rate in apparently healthy young to middle-aged working men

Background

It remains to be fully clarified whether there is a relationship between uncontrolled dyslipidemia and decline in estimated glomerular filtration rate (eGFR) in the general population. Therefore, this study’s aim was to test the association of dyslipidemia with changes in eGFR in apparently healthy working men.

Methods

We retrospectively examined the annual medical check-up list of 14,510 male workers aged 20–60 years with eGFR?≥?60 mL/min/1.73 m² at baseline, and then evaluated the association of the changes in the check-up parameters with a decline in eGFR during the 5-year observation period.

Results

Mean age and eGFR were 38.5 years and 82.3 mL/min/1.73 m² at baseline, respectively. Evaluated low-density lipoprotein cholesterol (LDL-C) (≥140 mg/dL) was a strong indicator of CKD development in participants (basal eGFR 60–90 mL/min/1.73 m²) without hypertension [odds ratio (95% confidence interval): 1.46 (1.12–1.90)] or diabetes mellitus (DM) [1.49 (1.23–1.82)]. When LDL-C normalized under 140 mg/dL during follow-up, the decline in eGFR was smaller in non-hypertensive participants [?5.9 (?14.4 to ?0.9) vs ?13.4 (?18.4 to ?4.5) mL/min/1.73 m², p?<?0.05]. There was an inverse correlation between change of LDL-C and decline in eGFR (p for trend <0.001).

Conclusion

Increased LDL-C levels are associated with the development of incident CKD and eGFR decline in young to middle-aged working men without hypertension and/or DM.

     

A clinical evaluation of renal amyloidosis in the Japan renal biopsy registry: a cross-sectional study

Background and aim

The available clinical data are limited in a rare glomerular disease, renal amyloidosis. We aimed to clarify the clinical features of renal amyloidosis from database of the Japan Renal Biopsy Registry (J-RBR).

Methods

We performed a cross-sectional study with database of the J-RBR of the Japanese Society of Nephrology. We identified 281 cases of renal amyloidosis from 20,997 cases enrolled into the J-RBR from 2007 to 2014. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were compared among the levels of ages, amount of urine protein excretion (AUPE) or CKD G stages.

Results

The prevalence of renal amyloidosis was 1.3 % (281/20,997). DBP significantly decreased in higher age quartiles (P = 0.034). SBP and DBP did not increase in the progression of AUPE levels and CKD G stages. In multiple regression analysis, eGFR was a significant independent factor for SBP in all cases and a subgroup without hypertensive agents. There was a reverse significant relationship between SBP and eGFR.

Conclusion

Blood pressure did not significantly increase in elderly and much proteinuric condition in renal amyloidosis. The progression of CKD and decrease of eGFR did not produce the higher SBP. The mechanism underlying these results remains unclear; however, they are unique features of renal amyloidosis. The couple of hypotensive and hypertensive conditions might produce no relationship between blood pressure and CKD stages.

     

Time-dependent risk factors associated with the decline of estimated GFR in CKD patients

Background

Targeting the modifiable risk factors may help halt the progression of CKD, thus risk factor analysis is better performed using the parameters in the follow-up. This study aimed to examine the time-dependent risk factors for CKD progression using time-averaged values and to investigate the characteristics of rapid progression group.

Methods

This is a retrospective cohort study enrolling 770 patients of CKD stage 3–4. Time-dependent parameters were calculated as time-averaged values by a trapezoidal rule. % decline of estimated GFR (eGFR) per year from entry was divided to three groups: <10 % (stable), 10–25 % (moderate progression), and ≥25 % (rapid progression). Multivariate regression analyses were employed for the baseline and the time-averaged datasets.

Results

eGFR decline was 2.83 ± 4.04 mL/min/1.73 m²/year (8.8 ± 12.9 %) in male and 1.66 ± 3.23 mL/min/1.73 m²/year (5.4 ± 11.0 %) in female (p < 0.001). % decline of eGFR was associated with male, proteinuria, phosphorus, and systolic blood pressure as risk factors and with age, albumin, and hemoglobin as protective factors using either dataset. Baseline eGFR and diabetic nephropathy appeared in the baseline dataset, while uric acid appeared in the time-averaged dataset. The rapid progression group was associated with proteinuria, phosphorus, albumin, and hemoglobin in the follow-up.

Conclusion

These results suggest that time-averaged values provide insightful clinical guide in targeting the risk factors. Rapid decline of eGFR is strongly associated with hyperphosphatemia, proteinuria, and anemia indicating that these risk factors should be intervened in the follow-up of CKD.

     

Development of Severe Hyperparathyroidism Despite Short-Term Renal Replacement Therapy

Background

We occasionally experience cases of severe secondary hyperparathyroidism (SHPT) that require parathyroidectomy (PTX) despite undergoing short-term renal replacement therapy (RRT). Because the characteristics of such cases have never been discussed, we aimed to elucidate the pathophysiology of severe SHPT after short-term RRT by retrospectively analyzing clinical data.

Methods

A total of 1013 patients with severe SHPT underwent PTX between January 2007 and April 2016 at Nagoya Daini Red Cross Hospital. Of these patients, 570 underwent RRT for ≥10 years (long RRT group) and 23 for ≤1 year (short RRT group). We retrospectively investigated and compared patient characteristics, preoperative data, subjective symptoms, and bone lesion incidence between the two groups.

Results

A higher proportion of subjects with congenital or hereditary diseases as primary disease for chronic kidney disease (CKD) (21.7% (5/23) vs. 6.3% (36/570); P = 0.016) and longer predialysis period (21.2 ± 14.0 vs. 10.1 ± 9.2 years; P < 0.001) were observed in the short RRT group than in the long RRT group. Furthermore, lower serum calcium and phosphate levels, heavier parathyroid glands, and severe bone lesions were observed in the short RRT group than in the long RRT group.

Conclusion

Severe SHPT after short-term RRT appeared to occur because of long-term CKD before initiating RRT. Therefore, treating mineral and bone disorders during the early CKD stage might prevent severe SHPT development before initiating RRT.