Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function

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Prospective Study of Serum 25-Hydroxyvitamin D Level, Cardiovascular Disease Mortality, and All-Cause Mortality in Older U.S. Adults

OBJECTIVES: To evaluate the association between serum 25‐hydroxyvitamin D (25(OH)D) levels and mortality in a representative U.S. sample of older adults. DESIGN: Prospective cohort from the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality files. SETTING: Noninstitutionalized U.S. civilian population. PARTICIPANTS: Three thousand four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000. MEASUREMENTS: Primary exposure was serum 25(OH)D level at enrollment. Primary and secondary outcomes were all‐cause and cardiovascular disease (CVD) mortality, respectively. RESULTS: During the median 7.3 years of follow‐up, there were 1,493 (44%) deaths, including 767 CVD‐related deaths. Median 25(OH)D level was 66 nmol/L. Adjusting for demographics, season, and cardiovascular risk factors, baseline 25(OH)D levels were inversely associated with all‐cause mortality risk (adjusted hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.98, per 10 nmol/L 25[OH]D). Compared with subjects with 25(OH)D levels of 100 nmol/L or higher, the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 (95% CI=1.14–2.94) and for levels of 25.0 to 49.9 nmol/L was 1.47 (95% CI=1.09–1.97). The association appeared stronger for CVD mortality (adjusted HR=2.36, 95% CI=1.17–4.75, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L) than for non‐CVD mortality (adjusted HR=1.42, 95% CI=0.73–2.79, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L). CONCLUSION: In noninstitutionalized older adults, a group at high risk for all‐cause mortality, serum 25(OH)D levels had an independent, inverse association with CVD and all‐cause mortality. Randomized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible.     

Rate of Kidney Function Decline and Risk of Hospitalizations in Stage 3A CKD

Background and objectives

Risk of hospitalizations is increased in patients with CKD. We sought to examine the association between rate of kidney function decline and risk of hospitalization in a cohort of patients with early CKD.

Design, settings, participants, & measurements

We built a cohort of 247,888 United States veterans who had at least one eGFR measurement between October 1999 and September 2003 and an additional eGFR between October 2003 and September 2004. We selected patients whose initial eGFR was between 45 and 59 ml/min per 1.73 m². Rate of eGFR change (in milliliters per minute per 1.73 m² per year) was categorized as no decline (>0), mild (0 to −1, and served as the referent group), moderate (−1 to −5), or severe (>−5) eGFR decline. We built survival models to examine the association between the rate of kidney function decline and the risk of hospitalization and readmission and linear regression to estimate length of hospital stay.

Results

Over a median observation of 9 years (interquartile range, 5.28–9.00), patients with moderate and severe eGFR decline exhibited a higher risk of hospitalizations (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.19 to 1.26; and HR, 1.33; 95% CI, 1.28 to 1.39, respectively). Among patients with moderate and severe eGFR decline, the association between the rate of decline and the risk of hospitalizations was more pronounced with an increased number of hospitalizations (P<0.01). Patients with moderate and severe eGFR decline had a higher risk of readmission (HR, 1.19; 95% CI, 1.13 to 1.26; and HR, 1.53; 95% CI, 1.43 to 1.63, respectively). Among patients with severe eGFR decline, the association between the rate of kidney function decline and the risk of readmission was stronger with an increased number of readmissions (P<0.01). Patients with moderate and severe eGFR decline experienced an additional length of stay of 1.40 (95% CI, 0.88 to 1.92) and 5.00 days per year (95% CI, 4.34 to 5.66), respectively.

Conclusions

The rate of kidney function decline is associated with a higher risk of hospitalizations, readmissions, and prolonged length of hospital stay.     

半胱氨酸蛋白酶抑制剂C与肾功能和心血管疾病

临床实践中普遍使用内源性血清物质估算肾小球滤过率,血清肌酐浓度最为广泛的应用,然而,某些时候肌酐测量过高估计肾小球滤过率。半胱氨酸蛋白酶抑制剂C是一种低分子量的肾小球滤过率内在标志,大量研究证明它在体内产生速率稳定,影响因素极少,是反映早期肾小球滤过功能受损的一个更理想、更可靠的指标,并且众多数据表明半胱氨酸蛋白酶抑制剂C在指导很多心血管疾病的诊断及治疗中有潜在的临床意义。现综述提出微环境炎症可能是半胱氨酸蛋白酶抑制剂C、肾功能和心血管疾病之间的关联之处。     

Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function

Background and objectives

Patients with CKD are more likely than others to have abnormalities in serum potassium (K⁺). Aside from severe hyperkalemia, the clinical significance of K⁺ abnormalities is not known. We sought to examine the association of serum K⁺ with mortality and hospitalization rates within narrow eGFR strata to understand how the burden of hyperkalemia varies by CKD severity. Associations were examined between serum K⁺ and discontinuation of medications that block the renin-angiotensin-aldosterone system (RAAS), which are known to increase serum K⁺.

Design, setting, participants, & measurements

A cohort of patients with CKD (eGFR<60 ml/min per 1.73 m²) with serum K⁺ data were studied (n=55,266) between January 1, 2009, and June 30, 2013 (study end). Serum K⁺, eGFR, and covariates were considered on a time-updated basis. Mortality, major adverse cardiovascular events (MACE), hospitalization, and discontinuation of RAAS blockers were considered per time at risk.

Results

During the study, serum K⁺ levels of 5.5–5.9 and ≥6.0 mEq/L were most prevalent at lower eGFR: they were present, respectively, in 1.7% and 0.2% of patient-time for eGFR of 50–59 ml/min per 1.73 m² versus 7.6% and 1.8% of patient-time for eGFR<30 ml/min per 1.73 m². Serum K⁺ level <3.5 mEq/L was present in 1.2%–1.4% of patient-time across eGFR strata. The median follow-up time was 2.76 years. There was a U-shaped association between serum K⁺ and mortality; pooled adjusted incidence rate ratios were 3.05 (95% confidence interval, 2.53 to 3.68) and 3.31 (95% confidence interval, 2.52 to 4.34) for K⁺ levels <3.5 mEq/L and ≥6.0 mEq/L, respectively. Within eGFR strata, there were U-shaped associations of serum K⁺ with rates of MACE, hospitalization, and discontinuation of RAAS blockers.

Conclusions

Both hyperkalemia and hypokalemia were independently associated with higher rates of death, MACE, hospitalization, and discontinuation of RAAS blockers in patients with CKD who were not undergoing dialysis. Future studies are needed to determine whether interventions targeted at maintaining normal serum K⁺ improve outcomes in this population.     

Factors Associated with Recovery of Renal Function following Radical Nephrectomy for Kidney Neoplasms

Background and objectives

Partial nephrectomy or radical nephrectomy is the standard of care for patients with kidney neoplasms, but surgery may result in loss of renal function. We sought to identify patient characteristics associated with renal functional recovery following radical nephrectomy.

Design, setting, participants, & measurements

We performed a retrospective study among 572 patients with kidney neoplasms who underwent RN between 2006 and 2013. The primary endpoint was recovery of postoperative eGFR to the preoperative level. We plotted the trajectory of each patient’s eGFR from their first postoperative visit up to 3 years after surgery. Cumulative incidence and competing risks regression estimated associations between patient and clinical characteristics and eGFR recovery, stratified by preoperative eGFR.

Results

Median age was 61.5 years; 68% of patients were male, and 89% were white. Overall, eGFR increased over time following an initial postoperative decrease. Median postoperative follow-up among survivors was 10.8 (minimum, 0.03; maximum, 36.0) months; during follow-up, 263 patients achieved eGFR recovery. Median time to eGFR recovery was 25.3 months. Two-year cumulative incidence of eGFR recovery was 49% overall and 44% and 58% among those with preoperative eGFR≥60 and <60 ml/min per 1.73 m², respectively (P<0.001). On multivariable analysis, younger age at surgery and female sex were significantly associated with a higher chance of eGFR recovery among patients with preoperative eGFR<60 ml/min per 1.73 m². Among patients with preoperative eGFR≥60 ml/min per 1.73 m², hypertension was significantly associated with a lower chance of eGFR recovery, whereas increased tumor size was significantly associated with a higher chance of eGFR recovery.

Conclusions

Overall, almost half of the patients in this study recovered to their preoperative eGFR by 2 years following surgery. Distributions of preoperative risk factors differed by preoperative eGFR, leading to distinct factors that were significantly associated with chance of eGFR recovery.     

Effect of Vitamin D Supplementation on Kidney Function in Adults with Prediabetes: A Secondary Analysis of a Randomized Trial

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维生素D与慢性肾脏病和肾移植

维生素D的主要作用是维持体内钙稳态.近期研究发现,除钙磷调节外,维生素D还对机体许多疾病的病理生理过程有重要影响.维生素D与慢性肾脏病的关系已为人们所熟识,其对肾移植受者移植肾的作用也被人们逐渐认识,本文将就此作一综述.     

Creatinine‐based estimation of glomerular filtration rate in patients with a Fontan circulation

Background: Patients with a Fontan circulation are at risk of renal dysfunction. We analyzed cross‐sectional data in pediatric and adult Fontan patients in order to assess the accuracy of commonly used serum creatinine‐based methods in estimating glo‐ merular filtration rate (GFR). Methods: A total of 124 Fontan patients (58 children, 66 adults) were enrolled across three study centers. Measurement of GFR (mGFR) using in vivo ^99mTc‐DTPA clear‐ ance was performed. Various serum creatinine‐based equations were used to calcu‐ late estimated GFR (eGFR). Results: Mean mGFR was 108 ± 28 mL/min/1.73 m² in children and 92 ± 20 mL/ min/1.73 m² in adults. Fourteen children (25%) and 28 adults (45%) had an mGFR <90 mL/min/1.73 m² . There was no significant correlation between mGFR and eGFR (Schwartz) in children (r = 0.22, P = .1), which substantially overestimated mGFR (bias 50.8, 95%CI: 41.1‐60.5 mL/min/1.73 m² , P < .0001). The Bedside Schwartz equation also performed poorly in the children (r = 0.08, P = .5; bias 5.9, 95%CI: −2.9‐14.6 mL/ min/1.73 m² , P < .0001). There was a strong correlation between mGFR and both eGFR (CKD‐EPI) and eGFR (MDRD) in adults (r = 0.67, P < .0001 in both cases), how‐ ever, both methods overestimated mGFR (eGFR(CKD‐EPI):bias 23.8, 95%CI: 20‐27.6 mL/min/1.73 m² , P < .0001; eGFR (MDRD):bias 16.1, 95%CI: 11.8‐20.4 mL/ min/1.73 m² , P < .0001). None of the children with an mGFR <90 mL/min/1.73 m² had an eGFR (Schwartz) <90 mL/min/1.73 m² . Sensitivity and specificity of eGFR (CKD‐EPI) and eGFR (MDRD) for mGFR <90 mL/min/1.73 m² in adults were 25% and 92% and 39% and 100%, respectively. Conclusions: This study identifies the unreliability of using creatinine‐based equa‐ tions to estimate GFR in children with a Fontan circulation. The accuracy of formulas incorporating cystatin C should be further investigated and may aid noninvasive sur‐ veillance of renal function in this population.     

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

Background and objectives

Elevations in N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.

Design, setting, participants, & measurements

N-terminal pro–B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.

Results

In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro–B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).

Conclusions

Elevated N-terminal pro–B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.     

Utility of a Score for Predicting Glomerular Filtration Rate Overestimation in Patients with Cardiovascular and Renal Diseases and Their Risk Factors

Objective We recently reported a novel score for the detection of glomerular filtration rate (GFR) overestimation using a creatinine-based equation. We examined the utility of this score in patients with cardiovascular/renal diseases and diabetes mellitus. Methods We enrolled 1,425 patients (65±15 years old; 37% women) who were admitted to our hospital for the management of cardiovascular and renal diseases and their risk factors. Overestimation of the GFR (OE) was defined as a creatinine-based GFR (eGFRcre) ≥120% of the cystatin C-based estimated GFR. The OE score was calculated as the sum of the scores for the body weight, hemoglobin concentration, and blood urea nitrogen (BUN)/serum creatinine (Scr), totaling 1 point if the body weight was <63.0 kg in men or <42.0 kg in women, 1 point if the hemoglobin concentration was <12.4 g/dL in men or <11.0 g/dL in women, and 1 point if the BUN/Scr was >26.5. Results The proportion of patients with OE was 14.2%. The score predicted OE with a sensitivity of 70.8% and a specificity of 99.6%, and the sensitivity was increased in patients ≥75 years old (88.3%) and decreased in diabetics (58.6%). When patients were divided into subgroups by the total score, the frequencies of OE were 8% (59/754), 14% (72/502), 38% (58/151), and 72% (13/18) in patients with scores of 0, 1, 2, and 3, respectively. Conclusion The OE score is useful for detecting elderly cases of cardiovascular and renal diseases in which eGFRcre overestimates the GFR, although its utility is limited in diabetics.     

Serum Concentrations of 25-Hydroxyvitamin D and Vitamin D-binding Protein in Elderly People

ABSTRACT Serum concentrations of 25-hydroxyvitamin D (25-OH-D) and vitamin D-binding protein (DBP) were measured in institutionalized and non-institutionalized elderly people. The institutionalized subjects were found to have low serum 25-OH-D in confirmation of other studies, but their serum DBP levels were similar to those found in non-institutionalized elderly subjects. Serum DBP concentrations were slightly higher in elderly females than in males, while no age dependence was found for DBP. Elderly people with protein-energy malnutrition who lived in their own homes had slightly reduced serum DBP and 25-OH-D levels. Elderly subjects with infections or other diseases causing acute inflammation, as indicated by an elevated serum haptoglobin and C-reactive protein, had normal levels of DBP.     

Function of the Isolated Perfused Kidneys from Young or Adult Rats with Post-Doca-Salt Hypertension

The function of isolated perfused kidneys in post-DOCA phase of DOCA-salt hypertension was evaluated in rats subjected to DOCA-salt treatment either from youth or only in adulthood. Post-DOCA-salt hypertension was more severe in young than in adult animals. Kidneys isolated from young post-DOCA-salt hypertensive rats had higher renal vascular resistance when compared to adult ones. Perfusion of isolated kidneys over a wide range of perfusion pressure (110–170 mm Hg) has shown similar decrease of glomerular filtration, filtration fraction, diuresis and natriuresis in both age groups of DOCA-salt treated groups. Perfusion pressure-sodium excretion curves had reduced slope and were shifted to the right in both hypertensive groups, indicating huge glomerular damage. Nevertheless, the relative difference in glomerular filtration and sodium excretion between hypertensive rats and age-matched normotensive controls was always greater in younger animals. These results suggest that the more pronounced changes in     

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population

Background and objectives

Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study.

Design, setting, participants, & measurements

Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance.

Results

In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29–57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m².

Conclusion

Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.     

149例慢性肾衰患者血脂水平及其与肾功能的相关性

目的探讨血脂水平对慢性肾衰患者肾功能的影响。方法检测149例慢性肾衰患者（观察组）和30例健康献血者（对照组）血脂[TG、TC、HDL—C、LDL—C、血肌酐（SCr）]水平,并分析上述指标与肾小球滤过率（GFR）的相关性。结果观察组TG、TC轻度升高,HDL—C明显下降,LDL—C明显升高。GFR与TG、TC无明显相关性,而与HDL-C水平呈明显正相关（r=0．21,P〈0．05）,与LDL—C水平呈显著负相关（r=-0．29,P〈0．01）。结论慢性肾衰患者存在明显的血脂代谢异常;其可能是加快肾脏功能损伤的重要危险因素。     

肾小球滤过率估算公式的发展改进及应用

肾小球滤过率(GFR)的准确评估对慢性肾脏病(CKD)的诊断、分期及判断预后均具有重大意义.由于实际GFR测定较为复杂,临床上常需依赖各种公式对GFR进行间接的估算.在过去的三十多年里,相继有多个用于GFR评估的公式问世.成人常用的GFR估算公式有Cockcroft-Gault公式、MDRD公式、CKD-EPI公式及其相应的改良公式.CKD-EPI公式可弥补MDRD公式在GFR较高时精确度不高的缺陷,因而被新的指南所推荐.此外,还有一些基于胱抑素CysC的GFR估算公式.本文对上述公式的发展沿革及各自的特点和影响因素作一综述.