Clinical and pathological features of six cases of sarcoidosis presenting with renal failure

Six patients with biopsy-proven renal sarcoidosis presented with renal failure of unknown origin; in none was the diagnosis of sarcoidosis initially considered. The serum creatinine concentration at the time of presentation ranged from 265 to 1380 μmol/l (3.0 to 15.6 mg/dl), with a mean of 787 μmol/l (8.9 mg/dl). Although only two patients were hypercalcemic at the time of presentation, the 24-hour urinary excretion of calcium was increased in three of the four patients in whom it was measured, and renal calculi were present in one case. Renal biopsy revealed interstitial nephritis and tubular atrophy in all cases, as well as nephrocalcinosis in three cases and noncaseating granulomas negative for acid-fast bacilli in four cases. In each patient steroid therapy led to a rapid improvement in renal function (mean post-treatment serum creatinine level 274 μmol/l [3.1 mg/dl]). The follow-up period ranged from 8 months to 8 years (mean 3.0 years). In three patients renal function remained stable with low-dose steroid therapy. In two cases recurrent hypercalcemia and deteriorating renal function accompanied steroid withdrawal but resolved with its reinstitution. In one additional case reversible deterioration in renal function accompanied tapering of the steroid dose; however, there was no hypercalcemia.This report emphasizes the importance of considering sarcoidosis in the differential diagnosis of acute renal failure of unknown origin. Long-term follow-up of such patients is essential, as relapse is common.     

Effects of ramipril and valsartan on proteinuria and renal function in patients with nondiabetic proteinuria

The renin-angiotensin system is involved in the progression of chronic renal disease of both diabetic and nondiabetic origin. The angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have been demonstrated to reduce urinary protein excretion and attenuate the development of renal injury. This prospective, randomized, 12-month study assessed the effects of ramipril (N = 23) vs. valsartan (N = 22) vs. combination of ramipril and valsartan (N = 26) on proteinuria, renal function and metabolic profile in 71 patients with nondiabetic proteinuria with normal or slightly impaired renal function. Monotherapy with ramipril or valsartan and combination of these two drugs significantly reduced proteinuria, serum creatinine, cholesterol and triglycerides as well as systolic and diastolic arterial blood pressure. There was no significant difference among three study groups according to reduction of arterial blood pressure, serum cholesterol and triglycerides. At one year, a significant reduction in serum creatinine was recorded in all three study groups, whereas at 3 and 6 months a statistically significant reduction in serum creatinine was only observed in patients on combination therapy. In addition, at 3 months the reduction of proteinuria was significantly greater in patients on combination therapy than in those on either monotherapy. These results indicated the combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to be more efficacious than either monotherapy in reducing proteinuria and serum creatinine level in the first 3 (proteinuria and serum creatinine) or 6 (serum creatinine) months of treatment.     

超微血流成像术用于肾移植患者术后评估的临床价值分析

目的:探讨超微血流成像术用于肾移植患者术后评估的临床价值。方法:选取我院2019年2月-2019年8月收治的60例肾移植患者的临床资料,根据术后恢复情况分为A、B、C三组,A组(27例,术后肾功能恢复良好)、B组(20例,术后发生过敏肾功能异常病变但治疗后肾功恢复正常)、C组(13例,术后血肌酐水平持续增高肾功能异常者),三组均采用超微血管流成像术检测血管指数,比较不同组患者的血管指数并分析其与血肌酐水平的关系。结果:三组患者的肾移植长径、前后径、左右径、皮质厚度、叶间动脉阻力指数比较无显著差异(P0.05)。C组患者的肾皮质血管指数(23.34±6.03%)明显低于A组(33.23±3.45%)、B组(31.23±4.23%)(P0.05)。肾功能异常患者肾皮质的血管指数较低,且随着血肌酐水平的升高而下降,两者呈显著负相关(r=-0.23,P0.05)。结论:超声微血流成像术用于肾移植患者术后评估可较好地反映肾皮质血供及术后肾功能的变化。     

卡托普利与坎地沙坦对老年糖尿病肾病患者肾功能的影响

目的:研究卡托普利联合坎地沙坦对糖尿病肾病患者肾功能的影响及临床疗效。方法:选择2014年5月-2015年5月我院收治的糖尿病肾病患者90例,根据治疗方法不同分为观察组和对照组。对照组给予卡托普利治疗,观察组在对照组基础上加用坎地沙坦治疗。观察并比较两组患者的临床疗效以及治疗前后空腹血糖、血尿素氮、血肌酐、24 h尿蛋白等水平的变化情况。结果:观察组的治疗总有效率为93.3%,对照组的治疗总有效率为84.4%;观察组患者的临床疗效显著高于对照组,但差异并不具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后的空腹血糖、血尿素氮、血肌酐及24 h尿蛋白水平均显著降低,差异具有统计学意义(P0.05);治疗后,观察组患者的空腹血糖、血尿素氮、血肌酐和24 h尿蛋白值均显著均明显低于对照组,差异均具有统计学意义(P0.05)。结论:卡托普利联合坎地沙坦治疗糖尿病肾病较单独采用卡托普利治疗能够更加有效的改善患者的临床症状,保护患者的肾功能,具有较好的临床疗效。     

Use of 5-Fluorocytosine in Patients with Impaired Renal Function

The plasma level and elimination of 5-fluorocytosine (5-FC) was measured in normal subjects and patients with impaired renal function. Prolongation of the half-life of the drug in renal failure has been confirmed. Renal clearance of 5-FC was about 75% of the creatinine clearance and a corresponding modification of drug dosage should be made in patients with renal insufficiency.     

Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis

BackgroundScarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998, that were also previously evaluated 2 and 5 years after the acute episode.MethodsIn this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria.ResultsComparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m² and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p = 0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed additional reduction of renal function using serum creatinine, eGFR and cystatin C.ConclusionsDuring the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur.     

Branched Renal Calculi

Surgical operation on 30 kidneys was carried out for branched renal calculi, with no operative mortality. Of 23 kidneys in which conservative surgical procedures were used, 83 percent are now stone-free. When all stones were successfully removed, cultures of urine were sterile in 80 percent of cases, but when fragments remained, no patient was infection-free. It was found that impaired renal function need not be a contraindication to surgical operation, and indeed that in five of seven patients with impaired renal function, serum creatinine levels either remained stable or improved. We believe that surgical removal is the most conservative management of branched renal calculi.     

Changes in renal function during bisphosphonate treatment of breast cancer patients

Renal function aberrations during bisphosphonate treatment is a well-known phenomenon. In our retrospective study we examined renal functions of 97 breast cancer patients with bone metastasis during their first year of bisphosphonate treatment i.e. (1) frequency of initial renal function alterations; (2) frequency of decreasing renal function during bisphosphonate treatment; (3) the connection between the laboratory findings and the renal function parameters measured at the beginning of bisphosphonate treatment. At the beginning of bisphosphonate treatment we found a surprisingly high rate (26.80%) of decreased creatinine clearance calculated by the Cockcroft-Gault formula. Decreased creatinine clearance at least once during bisphosphonate treatment has been found in 32.99% of the patients, and in 13.4% of the patients with decreased renal function parameters before bisphosphonates it remained decreased during the one-year period. Expected normal renal function is prognosticated by the renal function parameters and serum calcium level measured before starting bisphosphonate treatment. However, we could not demonstrate any connection between decreasing renal function and either the route of administration or the generation or type of bisphosphonates or the previous use of platinum compounds. Our analysis confirms the necessity of monitoring renal function before and during bisphosphonate treatment, and it is advisable to calculate the creatinine clearance in the upper quarter of the normal range of creatinine levels. In case of decreased renal function, change to a less nephrotoxic bisphosphonate or discontinuing the treatment is suggested. While our results are at variance with the published literature, the above-mentioned questions should be examined in a prospective trial.     

Apparent reduction of endogenous creatinine clearance by salicylate treatment.

A prospective study of nine patients with rheumatoid arthritis and 11 healthy volunteers who started salicylate treatment showed that in 18 of the 20 subjects creatinine clearance values fell the average being 25%. Serum creatinine concentration was increased by an average of 38%, although blood urea levels were unchanged. Since 51Cr-edetic acid clearance tests performed at the same time in 12 of the subjects were not affected, the fall in creatinine clearance was probably not due to impaired glomerular function, and salicylate ingestion may therefore invalidate the creatinine clearance test as an index of glomerular filtration rate. It is clearly important to inquire into the patient''s analgesic comsumption when using the creatinine clearance test to assess glomerular function.     

Renal function after long-term treatment with lithium.

Daily urine volumes, plasma creatinine concentrations, and creatinine clearance were measured in 106 patients with unipolar and bipolar affective disorders attending a "lithium" clinic. Urine volumes exceeded 3.51 in only six patients, plasma creatinine concentrations exceeded 150 mumol/1 (1.7 mg/100 ml) in only five, and creatinine clearance was below 50 ml/min in 16. Renal function was assessed by measuring creatinine clearance and renal tubular function, including response to 20 hours of water deprivation, in a representative sample of 30 patients from the lithium clinic and 30 psychiatric patients matched for age and sex who were taking other psychotropic drugs. Creatinine clearance and tubular function, including urine osmolality after water deprivation, were not significantly different between the two groups. Urinary excretion of arginine vasopressin (AVP), however, was much greater in the lithium-treated patients, who therefore had a diminished tubular responsiveness to AVP. The findings do not support suggestions that long-term lithium treatment results in seriously impaired renal function, renal damage, and polyuria. Compared with other series, however, the patients were being maintained with low serum lithium concentrations, which apparently area as effective prophylactically as higher concentrations.     

The incidence and clinical relevance of anti-HLA and/or MICA antibodies in patients with long-term survival renal allo-grafts

The purpose of this study was to analyze the incidence and clinical relevance of anti-HLA and/or MICA antibodies in renal allo-grafts transplant recipients with long-term renal survival (> 5 years). This retrospective study collected post-transplant serum samples from a total of 110 patients which were used to detect the incidence of anti-HLA and/or MICA antibodies as well as anti-HLA donor specific antibodies. Among these 110 patients, 72 patients had antibodies against HLA and/or MICA at the time of test, 61 had only anti-HLA antibodies, 31 had anti-MICA antibodies, and 38 were antibody negative. There was no difference in the number of patients developing antibodies against non-donor specific antibodies, donor specific antibodies, Class I donor specific antibodies, Class II donor specific antibodies or MICA antibodies between normal function group (serum creatinine level < 2.0 mg/dL) and dysfunction group (serum creatinine level > 2.0 mg/dL). For the serum creatinine level, estimated glomerular filtration rate and blood urea nitrogen level, patients with different antibodies were not statistically different to antibody-negative patients. Cox regression analysis showed that the type of transplantation and HLA mismatch number were significant negative risk factors for the development of anti-HLA (P < 0.05). Our results suggested that the anti-HLA antibody status has little impact on the renal graft function in the long-term survival allo-graft renal recipients.     

Clinical estimation of 1-alpha-hydroxycholecalciferol in treatment of patients with chronic renal failure]

31 adult patients (15 male and 16 female) with chronic renal failure were treated for 6 months with 1-alfa-hydroxycholecalciferol on a dose 0.25-2.0 micrograms/24 h. 15 patients with not very advanced renal failure (serum creatinine level 176.8-442 mumol/l) received conservative therapy (group I), 16 patients with serum creatinine value 884-1326 mumol/l were treated by intermittent hemodialysis (group II). The statistically significant decrease of serum alkaline phosphatase activity in group I and II (p < 0.01), the rise of serum calcium level in group I (p < 0.005) were determined. Half of the patients from both the groups stated the relief or disappearance of bone and joint pains and muscle weakness. Besides in group I significant decrease of creatinine clearance (p < 0.001) and increase of serum urea and creatinine value (p < 0.01) were noticed. On the basis of these results we can conclude that the treatment with 1-alfa-hydroxycholecalciferol, produced by "Polfa", ought to be introduced gradually with increasing doses and frequent monitoring of calcium-phosphate metabolism and renal function parameters.     

Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

Context

Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known.

Objective

We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma.

Methods

We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients.

Results

70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion.

Conclusion

Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective.     

Treatment of renal osteodystrophy with 1,25-dihydroxycholecalciferol.

Nine patients with renal osteodystrophy were tested for 6.5 to 35 months with 1,25-dihydroxycholecalciferol (1,25-DHCC). A close biochemical follow-up was performed during the first 6 months of treatment, including biweekly determinations of serum calcium, phosphorus, magnesium, alkaline phosphatase and creatinine levels. A bone biopsy, radiologic investigations and determinations of plasma levels of immunoreactive parathyroid hormone (IPTH) and intestinal absorption of calcium 47 were performed before and after the 6 months. Although the five patients with osteitis fibrosa showed a significant improvement, the four with predominantly osteomalacic lesions showed no response to treatment. These four had a normal initial plasma iPTH level, higher serum calcium levels than the other five patients, extreme sensitivity to 1,25-DHCC, with frequent episodes of hypercalcemia, and only a slightly increased serum alkaline phosphatase level, which remained unchanged during treatment. All but one of the patients, irrespective of the histologic abnormality, showed a decrease in the uptake of radionuclide by bone after treatment. The renal function of one patient, a man with long-standing stable renal failure who had not undergone dialysis, deteriorated during treatment.     

亲属活体供肾的病理改变及其临床相关性

目的 探讨亲属活体供肾的病理改变与类型,分析供肾病理改变与供体临床预后的相关性.方法 2007 年5 月至2008 年7 月完成59 例亲属活体供肾肾移植,供肾灌注后用Trucut 肾活检针(18 G)行肾下极穿刺活检,常规行光镜检查和免疫组化检查.供体术后观察血清肌酐、尿常规和尿生化等.结果 55 岁以下供者肾脏出现...     

Mechanisms Underlying Early Rapid Increases in Creatinine in Paraquat Poisoning

Background

Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR).

Methods and Findings

This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied.

Results

Forty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days.

Conclusion

Loss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition of creatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury.     

血液中肾损伤分子-1(KIM-1)和血清肌酐(SCr)对AKI的生物标志物作用

为了探讨血液中肾损伤分子-1 (KIM-1)和血清肌酐(SCr)的表达对外科术后急性肾损伤(AKI)的早期诊断价值,本研究选取医院内2018年3月至2019年3月进行外科手术的患者48例,分为AKI组患者即实验组12例,非AKI组患者即对照组36例,收集所有患者手术后0、3 h、6 h、9 h、12 h、24 h、48 h和72 h的血液样本,检测各个时间点血液中KIM-1和血清肌酐SCr水平,将血液中KIM-1与血清肌酐SCr水平进行相关统计学分析,绘制受试者工作特征曲线(ROC),探究并对比血液中KIM-1和血清肌酐的表达对外科手术后患者发生AKI的早期诊断价值。本研究数据显示,AKI组患者在手术后(3 h, 6 h, 9 h, 12 h)血液中KIM-1水平都高于0 h基准值,并且在6 h达到最大值;与此同时,AKI组患者手术后(0, 3 h, 6 h, 9 h)血液中KIM-1水平明显高于非AKI组患者。AKI组患者手术后血液中KIM-1 (0, 3 h, 6 h, 9 h)水平和手术后24 h的血清肌酐SCr水平呈正相关。本研究表明,3~9 h血液中KIM-1水平升高对患者外科手术后AKI的发生具备较高的诊断价值,血液中KIM-1可以作为早期诊断患者外科手术后发生AKI的一项生物标志物,且血清肌酐SCr的观测效率明显低于血液中KIM-1,可作为辅助诊疗手段。     

Letter: The clinical course of patients with analgesic nephropathy.

Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity.     

Elevated levels of serum creatinine: recommendations for management and referral

BACKGROUND: The potential benefits of earlier referral to a nephrologist of patients with elevated levels of serum creatinine include identifying and treating reversible causes of renal failure, slowing the rate of decline associated with progressive renal insufficiency, managing the coexisting conditions associated with chronic renal failure and facilitating efficient entry into dialysis programs for all patients who might benefit. METHODS: A subcommittee of the Canadian Society of Nephrology, which included representatives from family practice and internal medicine, conducted a MEDLINE search for the period 1966 to 1998 using the key words referral and consultation, dialysis, hemodialysis, peritoneal dialysis, renal replacement therapy and kidney diseases. Where published evidence was lacking, conclusions were reached by consensus. GUIDELINES: Earlier referral to nephrologists of patients with elevated creatinine levels is expected to lead to better health care outcomes and lower costs for both the patients and the health care system. All patients with newly discovered renal insufficiency (as evidenced by serum creatinine elevated to a level above the upper limit of the normal range of that laboratory, adjusted for age and height in children) must undergo investigations to determine the potential reversibility of disease, to evaluate the prognosis and to optimize planning of care. All patients with an established, progressive increase in serum creatinine level should be followed with a nephrologist. Adequate preparation for dialysis or transplantation (or both) requires at least 12 months of relatively frequent contact with a renal care team. Nephrologists should provide consultation in a timely manner for any patient with an elevated serum creatinine level. In addition, they should provide advice about what aspects of the condition require particularly urgent or emergency assessment. SPONSORS: This clinical practice guideline has been endorsed by the Canadian Society of Nephrology and the College of Family Physicians of Canada. Meeting, teleconference and travel expenses of the Referral Guideline Subcommittee were covered by The Momentum Program, a collaboration between Baxter Corp. and Janssen-Ortho Inc. However, the authors are solely responsible for the editorial content of this article.