Significant Recovery Of Renal Function Research Articles

MO1009: Early Switch from Fast IR-TAC Metabolizers to LCP-TAC Improves Renal Allograft Function

Abstract BACKGROUND AND AIMS In contrast to slow tacrolimus (Tac) metabolism, fast metabolism is associated with a more rapid decline in renal function [1–3]. Because the pharmacokinetics of LCP-Tac (LCPT) differ from those of immediate-release Tac (IR-Tac), we hypothesized that the estimated glomerular filtration rate (eGFR) of fast metabolizers, in particular, would be improved by switching from IR-Tac to LCPT. METHOD We included renal allograft recipients receiving a de novo immunosuppression with IR-Tac, mycophenolate and prednisolone. A Tac concentration-to-dose ratio (C/D ratio, surrogate for bioavailability) <1.05 ng/mL*1/mg defined fast metabolizers and ≥ 1.05 ng/mL*1/mg slow metabolizers one months after renal transplantation (RTx). All patients were switched to LCPT 1 month after transplantation or later. During a 3-year follow-up, Tac doses, C/D ratios, eGFR, infection and rejection rates were compared between the metabolizer groups. RESULTS Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0–253.1 versus 13.2 (1.2–172.8 months, P = .005). Tac doses were decreased by ∼65% in both groups after 12 months of conversion to LCPT. C/D ratios at 12 months increased from 0.66 (0.24–2.10) to 1.74 (0.42–5.43) (+163%) in fast and from 1.15 (0.32–3.60) to 2.75 (1.08–5.90) (+139%) in slow metabolizers. Fast metabolizers showed significant recovery of mean eGFR as early as one month after conversion (48.5 ± 17.6 versus 41.5 ± 17.0 mL/min/1.73 m²; P = .032) and at all subsequent time points. Conversion to LCPT did not result in relevant eGFR changes in slow metabolizers. Infection and rejection rates were low and did not differ between the groups before and after conversion. CONCLUSION Switching to LCPT increases the Tac bioavailability. This was associated with a significant recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx.

Early Robotic-Assisted Laparoscopic Pyeloplasty for Infants Under 3 Months With Severe Ureteropelvic Junction Obstruction.

Objective: To present our primary experience of robotic-assisted laparoscopic pyeloplasty (RALP) for severe ureteropelvis junction obstruction (UPJO) infants under 3 months.Methods: We performed a retrospective study of 9 infants under 3 months who underwent RALP for severe UPJO between April 2017 and March 2019 in our center. The severe UPJO was defined as infants with severe hydronephrosis (Society of Fetal Urology grades III or IV, anteroposterior diameter >3 cm or split renal function <40% or T 1/2 >20 min) involving bilateral, solitary kidney, or contralateral renal hypoplasia UPJO at the same time. All clinical, perioperative, and postoperative information was collected.Results: There were four bilateral UPJO cases, two solitary kidney UPJO cases and three unilateral UPJO with contralateral renal hypoplasia cases included. One single surgeon performed RALP on all of the infants. The mean age of the infants was 1.62 ± 0.54 months. The mean operative time was 109.55 ± 10.47 min. The mean estimated blood loss was 19.29 ± 3.19 ml, and the mean length of hospital stay was 5.57 ± 0.73 days. According to the ultrasonography results, all patients had a significant recovery of renal function at 12 months after the operation.Conclusions: To maximize the protection of renal function, early RALP is a safe and feasible option for the treatment of severe UPJO in infants under 3 months.

Treatment Effect of Regional Sodium Citrate Anticoagulation in Elderly Patients With High-Risk Bleeding Receiving Continuous Renal Replacement Therapy.

ObjectiveTo investigate the safety and efficacy of regional citrate anticoagulation (RCA) on elderly patients at high risk of bleeding after continuous renal replacement therapy (CRRT).MethodsA total of 31 patients at high risk of bleeding who received CRRT in the intensive care unit were collected. The patients were divided into RCA group (n = 17) and no anticoagulation group (NA, n = 14) according to whether RCA was used or not. The levels of creatinine (Cr), blood urea nitrogen (BUN), prothrombin time (PT), activated partial thromboplastin time (APTT), total calcium (tCa), ionized calcium ion (iCa2+), sodium ion (Na+), bicarbonate ion (HCO3−), tCa/iCa2+ ratio, and pH were observed after treatment. The filter use time, number of filters used, filter obstruction events, clinical outcomes, and safety evaluation indexes were compared post-treatment.ResultsAfter treatment, serum Cr and BUN levels, APTT and PT levels in the RCA group were significantly lower than the NA group. The tCa, iCa2+, HCO3−, tCa/iCa2+, and pH were within the normal range after RCA treatment while Na+ levels saw a significant increase. In the RCA group, the filter using time was significantly longer, with significantly reduced numbers of filter use within 72 h and filter disorder events. Additionally, patients in the RCA group showed significant recovery of renal function and a significant reduction in bleeding events and in-hospital mortality.ConclusionRCA treatment significantly improves clinical outcome of patients at high risk of bleeding after CRRT, safely and effectively prolongs the filter life and avoids coagulation incidences.

Inhibition of the P2X7 receptor improves renal function via renin-angiotensin system and nitric oxide on diabetic nephropathy in rats

AimTo evaluate the effects of P2X7 receptor blockade on renin-angiotensin system (RAS) in rats with diabetic nephropathy (DN). Main methodsWistar rats were unilaterally nephrectomized and received streptozotocin for diabetes mellitus (DM) induction; control animals (CTL) received the drug vehicle. The animals were submitted to P2X7 receptor silencing, forming the group (DM + siRNA). The animals were placed in metabolic cages for data collection and evaluation of renal function; at the end of the protocol, the kidney was removed for analysis of P2X7, renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin, thiobarbituric acid reactive substance levels (TBARS), nitric oxide (NO) and qualitative histological. Key findingsThe metabolic profile was attenuated in DM + siRNA vs. DM and there was a significant improvement in creatinine, urea and proteinuria levels in the same group. Renin expression was significantly decreased in DM + siRNA vs. DM. ACE and ACE2 were significantly reduced in DM + siRNA vs. DM. TBARS levels were decreased and NO showed an increase in DM + siRNA vs. DM, both significant. All histological alterations were improved in DM + siRNA vs. DM. SignificanceData have shown that although silencing of the P2X7 receptor did not decrease fasting glucose, it promoted an improvement in the metabolic profile and a significant recovery of renal function, revealing a protective action by the inhibition of this receptor. This effect must have occurred due to the inhibition of RAS and the increase of NO, suggesting that the use of P2X7 receptors inhibitors could be used as adjuvant therapy against DN progression.

PROGNOSTIC PARAMETERS FOR THE RECOVERY OF RENAL FUNCTION IN PATIENTS WITH OBSTRUCTIVE UROPATHY

Objective: The aim of this study was to determine the prognostic parameters for the recovery of renal function in patients with obstructive uropathy after the release of obstruction. Material &amp; methods: This is a retrospective cohort study. Secondary data from the patient's medical record was used to determine whether the ratio of blood urea nitrogen (BUN)/creatinine, hemoglobin, hyperkalemia, blood glucose, renal parenchymal thickness, and obstruction etiology are prognostic parameters for recovery of renal function in patients with obstructive uropathy after release of obstruction. Bivariate was used to analyze the data using Chi-square and Fisher's exact test with significance level of p&lt;0.05 to evaluate the significance. Results: Based on total of 66 research samples, it was found that renal parenchymal thickness was ≥10 mm (p=0.001), hemoglobin level was ≥10 mg/dL (p=0.001), and BUN/creatinine ratio was ≥10 (p=0.003), it had significant correlation with the recovery of renal function, meanwhile, obstruction etiology variable (p=0.566), and hyperkalemia (p=0.792) did not provide significant recovery of renal function. Conclusion: Renal parenchymal thickness, hemoglobin level, and BUN/Creatinin ratio are the prognostic parameters for recovery of renal function after release of obstruction.

Pathogenetic justification of possibility of antidiuretic hormone use in incontinent women

Hypothesis/aims of study. Urine incontinence seems to include several pathogenetic forms, as efficient therapy is provided by different medications. Commonly used in the treatment of female patients with overactive bladder and nocturnal polyuria is desmopressin which normalizes the water excretion of the kidney, which is disturbed by a presumed inverted rhythm of vasopressin secretion in these patients. The current analysis was undertaken to evaluate the clinical efficiency of desmopressine in incontinent patients with nocturnal polyuria and polyuria.&#x0D; Study design, materials and methods. A total of 84 patients with complaints of urinary incontinence, polyuria (24-urine volume of 40 mL/kg bodyweight or above) or nocturnal polyuria (nocturnal volume/24-h urine volume of 0.33 or above) and 14 control subjects were included. Mean patient age was 43.6 ± 4.6 years, in control subjects 38.5 ± 6.4 (p &gt; 0.05). All participants performed 24h-urinecollection to determine the voided volumes and the levels of creatinine, osmolality, sodium, magnesium and potassium for each sample. A blood sample was taken during the 24-urinecollection to determine the levels of creatinine, osmolality, sodium, magnesium and potassium. The examination of patients with polyuria and nocturnal polyuria was performed twice: in the initial state and one month after the start of treatment with optimal dose of desmopressin. Optimal dose was established through an open-label dose-titration using 0.1 mg, 0.2 mg and 0.4 mg of desmopressin (Minirin). Safety parameters assessed included incidence of adverse events, vital signs and serum sodium levels.&#x0D; Results. In patients with polyuria and nocturnal polyuria the glomerular filtration rate was normal, whereas diuresis and solute (sodium, magnesium, potassium) excretion in night samples in nocturnal polyuria and both in night and day samples in polyuria were increased. The higher diuresis and the higher solute excretion observed in nocturnal polyuria and polyuria are accompanied by an increase of free water reabsorption. In nocturnal polyuria and polyuria a high correlation was found between the free water reabsorption and solute excretion. This occurs against the background of the high night and day osmotic concentration. The statistically significant recovery of renal function occurred in 12 incontinent women with polyuria and 18 with nocturnal polyuria. In these papients there was a statistically significant decrease in diuresis, osmolar clearance and excretion of sodium, potassium and magnesium.&#x0D; Concluding message. As desmopressin affects cells of the thick ascending limb of Henle’s loop, it is likely that nocturnal polyuria and polyuria result from a disturbed regulation of the function of these cells. Normalization can be achieved by desmopressin administration to stimulate V2-receptors, which increase water permeability and water reabsoption in collecting ducts as well as ion reabsorption by cells of the thick ascending limb of Henle’s loop.

Correction of renal function by desmopressin and diclofenac in incontinent women with nocturia

The purpose of this study was to evaluate the clinical efficiency of desmopressine and diclofenac in incontinent patients with nocturnal polyuria and polyuria. A total of 277 patients ≥18 ≤ 55 years of age with complaints of urinary incontinence were included. 143 women had stress incontinence, 43 — urge incontinence and 91 — mixed incontinence. The overall prevalence of nocturia was 34.7 ± 2.9% (96 women).The frequency of poliuriya was 7 ± 2.1 % in stress incontinence, 11.6 ± 4.9 % in urge incontinence and 9.9 ± 3.1 % in mixed incontinence (p > 0.05). The frequency of nocturnal polyuria was 17.5 ± 3.2% in stress incontinence, 27.9 ± 6.8% in urge incontinence and 25.3 ± 4.6 % mixed incontinence (p > 0.05). Patients were randomized to receive either desmopressin or diclofenac in a double — blind fashion. The statistically significant recovery of renal function occurred in 8 incontinent women with polyuria and 19 with nocturnal polyuria who received diclofenac and in 12 incontinent women with polyuria and 18 with nocturnal polyuria who received desmopressin (Minirin). Refs 5. Figs 12. Table 1.

Substantial Recovery of Renal Function Is Uncommon Early Post Cardiac Transplant Irrespective of Pre-Transplant LVAD Support

Purpose Marked early recovery of renal function (RRF) is common after LVAD placement, with nearly half of patients experiencing ≥ 50% improvement in GFR in the first several weeks. However, this substantial RRF has not been observed early post-transplant (Tx). It is possible that the negative effects of acute calcineurin inhibitor (CNI) nephrotoxicity negate the improvement in GFR that would otherwise be seen with RRF post-Tx. If this hypothesis is correct, and given the fact that bridge-to-Tx LVAD patients should have already experienced RRF, acute CNI nephrotoxicity should act unopposed in these patients resulting in a large reduction in GFR. Methods and Materials A random sample of cardiac transplants at our center, oversampled for LVADs, with serial creatinine levels available were reviewed (n=138). Significant RRF was defined as a ≥50% improvement in GFR. Results The incidence of significant RRF was only 10.4% at 30 days and the mean GFR of the cohort was worse at all post-Tx time points compared to baseline (Figure). The magnitude of GFR deterioration was not different between patients with (n=65) or without (n=73) a pre-tx LVAD (p-interaction=0.51, Figure). At 30 days, decreases in GFR were similar between patients with CNI levels above or below the median (-1.2%, ± 35.1% vs. -2.6% ± 49.6%, p=0.86), both in patients with (p=0.69) and without (p=0.79) a pre-Tx LVAD. [ figure 1 ] Conclusions Meaningful RRF appears to be uncommon, even early post-Tx before chronic CNI nephrotoxicity is apparent. This finding is not significantly influenced by pre-Tx LVAD support or early CNI levels. Further research is needed to better understand changes in renal function following advanced therapies.

Treatment of atypical uraemic syndrome in the era of eculizumab.

Treatment of atypical uraemic syndrome in the era of eculizumab.

Bilateral renovascular disease with cardiorenal failure: intervene early or watch and wait?

Although, atherosclerotic renovascular disease (ARVD) is an important cause of acute pulmonary oedema (APO) and congestive heart failure (CHF) it is unclear whether best treatment for ARVD with APO or CHF should be medical therapy only or medical therapy with revascularization.1 The randomized controlled trials do not help here as they exclude heart failure.2 Evidence in favour of revascularization comes from case reports3 and observational studies of patients with APO4–6 and CHF7,8 with impressive improvements reported in heart failure symptoms, blood pressure and renal function following revascularization. The question therefore is how to identify such patients and whether to intervene early or watch and wait. Against this background we report a patient with bilateral renal artery stenoses and APO who declined intervention at presentation, and did well for 4 years before representing with cardiorenal failure requiring dialysis. Intervention even at this late stage led to a significant recovery of renal function. A 73-year-old woman presented in 2002 with pulmonary oedema due to acute coronary syndrome with Troponin I 17.5 ng/ml (normal 0–1). Serum creatinine was raised at 256 µmol/l (eGFR 17 ml/min). There had been no previous measurement of renal function. Both kidneys were 8 cm in bipolar diameter and CT renal angiogram …

Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities

Tenofovir, a widely prescribed antiretroviral medication for treatment of HIV-1 infection, is infrequently associated with renal dysfunction and biopsy findings of acute tubular necrosis. We examined the clinical and pathological findings in 13 cases of tenofovir nephrotoxicity (7 men and 6 women, mean age of 51.1±9.6 years). Patients received tenofovir therapy for a mean of 19.6 months (range, 3 weeks to 8 years; median 8 months). Nine patients presented with acute kidney injury, and four had mild renal insufficiency with subnephrotic proteinuria. Mean baseline serum creatinine was 1.3±0.3 mg/dl, reaching 5.7±4.0 mg/dl at the time of biopsy, with mean proteinuria of 1.6±0.3 g/day. Glycosuria was documented in seven patients, five of whom were normoglycemic. Renal biopsy revealed toxic acute tubular necrosis, with distinctive proximal tubular eosinophilic inclusions representing giant mitochondria visible by light microscopy. Electron microscopy showed mitochondrial enlargement, depletion, and dysmorphic changes. Clinical follow-up after tenofovir discontinuation was available for 11 of 13 patients (mean duration 13.6 months). Significant recovery of renal function occurred in all patients, including four who required transient hemodialysis. Our study shows that tenofovir nephrotoxicity is a largely reversible form of toxic acute tubular necrosis targeting proximal tubules and manifesting distinctive light microscopic and ultrastructural features of mitochondrial injury.

Reversal of acute renal failure by kidney revascularisation

To assess whether acute renal failure, due to total or subtotal renal artery occlusion, can be reversed by kidney revascularisation. A retrospective review of surgery for kidney salvage in anuric patients at a University Hospital. From 1983 to 1993, eight patients were operated on for occlusive renal artery disease as a cause of acute renal failure, requiring preoperative haemodialysis. On admission the mean serum creatinine was 40 mg/l (354 mumol/dl). The oligoanuria lasted from 12 h to 3 weeks. Renal length of 8 cm or more and visualisation of a patent distal renal artery branches on aortography were arguments that return of renal function could be expected after revascularisation of these non-functioning kidneys. Revascularisation restored immediate urine flow in six cases, with no further need for dialysis in four. Two patients remained oliguric despite successful reperfusion. One of them could be weaned from dialysis after 1 month. Two patients died postoperatively. Five of the eight patients left the hospital with restored renal function. Patients with acute renal function deterioration due to ischemia of a single or both kidneys can benefit from prompt revascularisation, with significant recovery of renal function in most of them.

Can immunosuppressive drugs slow the progression of IgA nephropathy?

The role of immunosuppressive drugs in the treatment of IgA nephropathy (IgAN) remains controversial. The effect of treatment with prednisolone and azathioprine on the clinical course of patients with IgA nephropathy is described in this retrospective study. One hundred and fourteen patients, 66 treated (age 13-77 years) and 48 untreated (age 15-64 years), were evaluated. The two groups of patients differed significantly with respect to heavier proteinuria (median 3.6 g/day, range 0.2-18 g/day), lower serum albumin level (< 40 g/l) and more severe renal histopathological involvement in the treated group (P < 0.01). Oral prednisolone 40 mg/day and azathioprine 2 mg/kg BW/day was commenced initially and after gradual tapering was continued at low dose (5 mg/day) for a median duration of 24 months (range 12-98). The median duration of follow-up was 46 months (range 12-180). The clinical course was defined as progressive or non-progressive on the basis of serial serum creatinine (Scr). Of the patients who presented with renal impairment (Scr > 110 mumol/l), a non-progressive course was observed in 79.5% patients of the treated group (n = 39), while only in 36% of the untreated group (n = 22), the difference was statistically significant (P < 0.001). Slopes of reciprocal of Scr versus time were also calculated by linear regression analysis to represent the trend of renal function for patients who had had 3 or more years follow-up (n = 101). An analysis of variance of these trends in patients with renal impairment at presentation (n = 51) showed significant recovery of renal function in the treated group (n = 33) and a decline of renal function in the untreated group (n = 18, P = 0.004). There was no significant effect of the treatment on proteinuria. The histopathological features that favoured response to the treatment were mesangial proliferation, capsular adhesions and interstitial infiltration on light-microscopy, C3 and fibrin deposits on immunofluorescence (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Successful Treatment of Mitomycin C-Associated Hemolytic Uremic Syndrome by Plasmapheresis

Therapeutic attempts have generally failed to reverse the rapid progression of renal failure after mitomycin C (MMC)-induced hemolytic uremic syndrome (HUS). A patient who developed HUS after MMC and who showed pathologic changes in the kidney consistent with thrombotic microangiopathy is reported. Treatment with plasmapheresis was followed by a favorable outcome and significant recovery of renal function. Accordingly, this therapeutic modality should be considered for patients with MMC-induced HUS.

Recovery in Malignant Hypertension Presenting as Acute Renal Failure

Malignant hypertension may present occasionally with acute renal failure. Seven patients with this syndrome were admitted to the Renal Unit of the Royal Infirmary, Glasgow, between 1977 and 1981 giving an estimated incidence of one per million of the population per year. All the patients smoked and all had features of microangiopathic haemolytic anaemia. Renal biopsies showed arterial subintimal changes with relative sparing of glomeruli in each case. Good control of blood pressure led to significant recovery of renal function in five of the seven patients after 10-44 days of peritoneal dialysis. Renal function improved progressively over the first year and the improvement has been sustained for an average of 24 months (range 15-62 months). Mean serum creatinine when last measured was 248 mumol/l (range 125-350 mumol/l). These results confirm previous reports of recovery of renal function in patients presenting with acute renal failure and malignant hypertension. The proportion of patients who improve may be higher than has been generally recognised, and recovery may last several years. The pathogenesis of the renal failure is discussed.