Persistent Renal Impairment Research Articles

A retrospective study of short- and long-term effects on renal function after acute renal infarction

Purpose: Acute renal infarction is often missed or diagnosed late due to its rarity and non-specific clinical manifestations. This study analyzed the clinical and laboratory findings of patients diagnosed with renal infarction to determine whether it affects short- or long-term renal prognosis. Methods: We retrospectively reviewed the medical records of 100 patients diagnosed as acute renal infarction from January 1995 to September 2012 at Gyeongsang National University Hospital, Jinju, South Korea. Results: Acute kidney injury (AKI) occurred in 30 patients. Infarct size was positively correlated with the occurrence of AKI (p = 0.004). Compared with non-AKI patients, AKI occurrence was significantly correlated with degree of proteinuria (p < 0.001) and the presence of microscopic hematuria (p = 0.035). AKI patients had higher levels of aspartate transaminase (p < 0.001), alanine transaminase (p < 0.001), and lactated dehydrogenase (p = 0.027). AKI after acute renal infarction was more common in patients with chronic renal failure (CRF) (eGFR < 60 mL/min), compared with non-CRF patients, whose baseline eGFR was >60 mL/min (p = 0.003). Most patients recovered from AKI, except for seven patients (7%) who developed persistent renal impairment (chronic kidney disease progression) closely correlated with magnitude of infarct size (p = 0.015). Six AKI patients died due to combined comorbidity. Conclusions: AKI is often associated with acute renal infarction. Although most AKI recovers spontaneously, renal impairment following acute renal infarction can persist. Thus, early diagnosis and intervention are needed to preserve renal function.

Effect of remote ischaemic conditioning on contrast-induced nephropathy in patients undergoing elective coronary angiography (ERICCIN): rationale and study design of a randomised single-centre, double-blind placebo-controlled trial

BackgroundContrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is an important cause of morbidity/mortality following coronary angiographic procedures in high-risk patients. Despite preventative measures intended to mitigate the risk of CIN, there remains a need for an effective intervention. Remote ischaemic conditioning (RIC), where non-injurious ischaemia is applied to an arm prior to the administration of contrast, has shown promise in attenuating CIN but its effectiveness in preserving long-term renal function is unknown, which will be studied as part of the effect of remote ischaemic conditioning against contrast-induced nephropathy (ERICCIN) trial. (http://Controlled-trials.com Identifier: ISRCTN49645414.)MethodsThe ERICCIN trial is a single-centre, randomised double-blinded placebo-controlled trial which plans to recruit 362 patients who are at risk of CIN, defined by pre-existent renal impairment (estimated glomerular filtration rate <60 ml/min/1.73 m2), over a period of 2 years. Patients will be randomised to either control or RIC consisting of 4, 5 min 200 mmHg balloon-cuff inflation/deflations, to the upper arm. The primary endpoint will be the development of CIN (>25 % of eGFR, or rise of creatinine of >44 μmol/l) at 48 h. A key secondary endpoint will be whether RIC impacts upon persistent renal impairment over the 3-month follow-up period. Additional secondary endpoints include the measurement of serum neutrophil gelatinase-associated lipocalin and urinary albumin at 6, 48 h and 3 months following administration of contrast.ImplicationsFindings from ERICCIN trial will potentially demonstrate that RIC attenuates contrast-induced acute and chronic kidney injury and influence future clinical practice guidelines in at-risk patients undergoing coronary angiographic procedures.

Novel Urinary Biomarkers in Detecting Acute Kidney Injury, Persistent Renal Impairment, and All-Cause Mortality Following Decongestive Therapy in Acute Decompensated Heart Failure

BackgroundNew urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18), are proposed to allow a more reliable early diagnosis and prognosis of acute kidney injury (AKI) in acute decompensated heart failure (ADHF). Our aim was to compare the predictive value of urinary NGAL, KIM-1, and IL-18 for the occurrence of AKI, persistent renal impairment, and mortality in ADHF. Methods and ResultsEighty-three patients admitted for ADHF were analyzed. Urinary creatinine (Cr), NGAL, KIM-1, and IL-18 were measured at baseline. Serum Cr was measured daily during the next 4 days and again at outpatient follow-up after 6 months. Mortality data were prospectively collected. Urinary NGAL, KIM-1, and IL-18 were modestly correlated with each other (Spearman ρ ≤0.61) and poorly correlated with estimated glomerular filtration rate (eGFR; Spearman ρ ≤0.28). None predicted AKI, defined as a 25% decrease in eGFR, during the index hospitalization, but urinary IL-18/Cr was the strongest predictor of persistently elevated serum Cr ≥0.3 mg/dL after 6 months compared with baseline (area under the receiver operating characteristic curve 0.674; P = .013). Urinary IL-18 was also significantly associated with all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.16–1.87; P = .001). ConclusionsLike urinary NGAL, urinary KIM-1 and IL-18 are relatively modest predictors of AKI in ADHF. Among these novel renal biomarkers examined, further investigations regarding the prognostic value of urinary IL-18 are warranted.

ECMO as a Bridge to Decision in “Crash an Burn” Patients: 8-Years Experience

Purpose Treatment of refractory cardiogenic shock with VAD or transplantation is controversial. The aim of our study was to evaluate ECMO support as a bridge to decision in “crash and burn patients” through our 8-years experience. Methods and Materials From June 2003 to December 2011, 124 patients received an ECMO for refractory cardiogenic shock, 26 out-hospital cardiac arrests were excluded from our study. Median age was 43 years, range from 11 to 73 years. Primary diagnoses were postcardiotomy failure (29.6%), end stage heart failure (18.4%), acute ischemic cardiomyopathy (17.4%), primary graft failure (12.2%), myocarditis (5.1%) and others (17.3%). ECMO was used in in-hospital arrest in 37.8% of cases. Peripheral femoro-femoral ECMO was mainly implanted (79.6%), a “central ECMO” was used in 20 patients. Results The median duration of ECMO support was 4.5 days (12 hours to 82 days). Mortality while supported with ECMO was 50% (40 patients) with a median support time of 2 days. Weaning from ECMO was achieved through cardiac recovery (57.7%), heart transplantation (26.5%), VAD implantation (14.1%). Most of the patients were weaned between the 4th and the 11th days of support (87.5%). Survival was 82.7%, 61.5% and 71.4% in case of cardiac recovery, heart transplantation or VAD implantation respectively. Stroke and persistent renal function impairment were significant risk factors with OR: 4.940 [2.274– 10.732], p Conclusions ECMO brings promising results as a bridge to decision in end stage refractory cardiogenic shock patients. Persistent renal function failure while supported with ECMO was associated with poor outcome. Further studies are needed to build appropriate risks score to better determine issues for patients supported with ECMO.

Recurrent Membranoproliferative Glomerulonephritis After Second Renal Graft Treated With Plasmapheresis and Rituximab

We present a case of a 45-year-old man who suffered from idiopatic membranoproliferative glomerulonephritis (MPGN) in the native kidney that relapsed after his first and second renal grafts. The patient was diagnosed in 1990 with lobular MPGN type I, receiving his first renal graft in 1996. In 2001, a biopsy showed recurrence of MPGN type I (rMPGN). He underwent a second renal graft in 2008. In January 2010, he experienced increased proteinuria and creatinine. Upon electron microscopy of a renal graft biopsy we diagnosed a new rMPGN. At the time of the biopsy, complement levels were normal, although C3 and C4 decreased further. We administered 12 plasmapheresis (PP) sessions and four doses of rituximab. Due to persistent renal impairment, we performed a new biopsy 3 months later, showing less severity of the acute lessions. He received a new cycle of treatment (PP + rituximab). One year later, his renal function was stable with a creatinine ranging between 2 and 2.5 mg/dL and a protein/creatinine ratio less than 1 mg/mg. We concluded that the treatment stopped the disease progression.

Cardiorenal Syndromes and Sepsis

The cardiorenal syndrome is a clinical and pathophysiological entity defined as the concomitant presence of renal and cardiovascular dysfunction. In patients with severe sepsis and septic shock, acute cardiovascular, and renal derangements are common, that is, the septic cardiorenal syndrome. The aim of this paper is to describe the pathophysiology and clinical features of septic cardiorenal syndrome in light of the actual clinical and experimental evidence. In particular, the importance of systemic and intrarenal endothelial dysfunction, alterations of kidney perfusion, and myocardial function, organ “crosstalk” and ubiquitous inflammatory injury have been extensively reviewed in light of their role in cardiorenal syndrome etiology. Treatment includes early and targeted optimization of hemodynamics to reverse systemic hypotension and restore urinary output. In case of persistent renal impairment, renal replacement therapy may be used to remove cytokines and restore renal function.

Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan

Thrombotic microangiopathy (TMA) co-existing with SLE is rarely reported. This study aimed to investigate the triggering factors, clinical features and outcomes of SLE patients with TMA in Northern Taiwan. Twenty-five TMA cases out of 2461 SLE patients admitted to Taipei Veterans General Hospital, between 2000 and 2010, were enrolled. When TMA occurred, 16 (64.0%) patients had infection; 22 (88.0%) were in an active disease state with a SLEDAI score >10. Among the infection group, 13 (81.3%) had an increase in the SLEDAI score of ≥ 4. We found that older age (≥ 50 years), low platelets (≤ 20,000/nm(3)), presence of infection, acute renal failure (ARF) or four or more TMA features were independent risk factors for persistent haematological abnormalities (P < 0.05); older age (≥ 50 years) and a high reticulocyte index (>2%) were the risk factors for persistent renal function impairment (P < 0.05). The overall mortality rate was 52.0% (13 out of 25); older age (≥ 40 years), low complement value, presence of infection (P < 0.001), two or more infection sources, ARF and four or more TMA features were the statistically significant factors contributing to a higher mortality rate. Patients receiving plasma exchange seven times or more had a significantly higher rate of improvement in renal function and haematological abnormalities. Our study showed that infection was one of the major triggers for the flare-up of SLE disease activity and occurrence of TMA in SLE. Infection is also a strong risk factor for outcome in SLE patients with TMA. Plasma exchange can be considered as an adjuvant treatment modality.

Use of Lenalidomide May Surmount the Adverse Prognosis Induced by Renal Impairment In Patients (pts) with Relapsed/Refractory Multiple Myeloma (MM)

AbstractAbstract 3042 Introduction:Current goals in MM treatment are to achieve prolonged remission- and treatment-free-intervals and to transform the disease into an indolent course. Renal impairment is a dreaded complication in MM and has formerly been associated with decreased progression free- (PFS) and overall-survival (OS) - at least with standard-MM-agents. Lenalidomide is an effective novel substance, recently suggested to overcome the adverse prognostic impact of renal impairment in MM to a similar extent as other agents, therefore the current study was undertaken to further evaluate the impact of lenalidomide treatment on PFS and OS of MM pts with varying degrees of renal impairment. Methods:Forty-five consecutive MM pts received lenalidomide with dose modification according to current guidelines in G1-4 treatment groups (G1: lenalidomide 25mg+dexamethasone (dex) 40mg [n=19]; G2: lenalidomide 25mg+low-dose dex [n=10]; G3: lenalidomide 10mg [n=11]; G4: lenalidomide 10–15mg plus chemotherapy [n=5]) in our department between 2006 and 2010. Serum creatinine and eGFR were determined before lenalidomide treatment and after 1, 3 and 6 months. Renal function was defined via NKDOQI guidelines and response according to EBMT. Results:The median pt age was 66 years (range: 44–78), with predominantly stage II/III disease according to Durie-Salmon (97%) and ISS (71%). Pretreatment before lenalidomide initiation was substantial: ≥2 previous therapy lines had been performed in 71% and autologous or allogeneic SCT in 49% and 11% of pts, respectively. Lenalidomide induced an overall response rate (ORR: CR+PR) in 27% (n=12) and clinical benefit rate (CBR=CR+PR+MR) in 37% (n=14). Median PFS and OS for all pts were 13 and 25 months, respectively, which is consistent with the results of both lenalidomide/dex-FDA-approved studies, albeit our pt cohort was older and more pretreated. Lenalidomide was well tolerated as previously reported. Although baseline renal function appeared normal with a median creatinine of 1.0mg/dl (range: 0.6–2.7), mild renal impairment was readily detectable via eGFR measurement (median 80ml/min/1.73m2; range: 25–119). Of note, eGFR <90 and <60ml/min/1.73m2 before lenalidomide-initiation was prominent, with 64% and 29%, respectively. Within various eGFR groups of ≥ vs. <90, 80, 70, 60 and 50ml/min/1.73m2, and creatinine groups of ≥ vs. < 0.9, 1.0, 1.1, 1.3 and 1.4mg/dl median PFS as well as 1- and 2-year PFS rates were similar in pts without or with renal impairment. With eGFR-changes of 10ml/min/1.73m2 and serum creatinine-changes of 0.1mg/dl, hazard ratios (HR) were 0.973 (95% CI: 0.849–1.115, p=0.6927) and 0.989 (95% CI: 0.923–1.059, p=0.7538) for PFS, respectively. For OS, HR were 0.839 (95% CI: 0.708–0.994, p=0.0421) and 1.047 (95% CI: 0.972–1.128, p=0.2253), respectively. This data and our HR suggest that large PFS and OS differences under lenalidomide treatment were unlikely existing between pts with vs. without renal impairment, albeit this does not exclude smaller differences detectable with larger pt scrutiny. In order to also determine reasons for and the implications of initial eGFR declines as compared to pts with improved renal function under lenalidomide, we compared pts who displayed decreasing vs. increasing eGFR. After 1 month of treatment, we observed no differences in specific pt characteristics, but notably more pts staying longer on lenalidomide-therapy and showing an ORR of 42% vs. 20% with decreasing vs. increasing eGFR, respectively. After 6 months, ORR in pts with decreased vs. increased eGFR was 8% vs. 47%, respectively, suggesting that an initial eGFR decline does not impair therapy efficacy, whereas after 6 months the group comparison suggested that pts with persistent renal impairment constitute a pt group with a more unfavourable prognosis. Conclusions:Our results underline that treatment with lenalidomide is feasible and well tolerated in elderly and intensively pretreated MM pts, including pts with renal impairment. We suggest that consequent measurement of eGFR - rather than solely via traditional serum creatinine - may predict therapy response. Group comparison of different eGFR and creatinine subgroups indicated that lenalidomide can reverse the adverse prognosis of renal impairment in MM pts with hematological and renal treatment response. Disclosures:Kleber:Celgene: educational grant. Engelhardt:celgene: educational grant.

The Effects of Adenosine A 1 Receptor Antagonism in Patients With Acute Decompensated Heart Failure and Worsening Renal Function: The REACH UP Study

Background Worsening renal function (WRF) portends a poor prognosis, and recent deterioration in creatinine might identify patients with elevated intrarenal adenosine in whom adenosine A 1 antagonism may improve renal hemodynamics and function. The purpose of this pilot study was to assess whether rolofylline, an adenosine A 1 antagonist (A 1RA), would facilitate diuresis while maintaining renal function in patients with acutely decompensated heart failure (ADHF) and recent WRF. Methods and Results Seventy-six patients with ADHF, volume overload, and recent renal deterioration received rolofylline (30 mg, n = 36) or placebo (n = 40) for 3 days. Rolofylline did not demonstrate a beneficial effect on the primary end points of worsening heart failure or renal function after admission or death or readmission within 30 days. Similar proportions of patients receiving rolofylline (33%) and placebo (30%) were treatment failures within 30 days. However, persistent renal impairment (through Day 14) tended to be less common with rolofylline (6%) than placebo (18%). At Day 14, 11 patients receiving placebo and 13 patients receiving rolofylline had a decrease in creatinine ≥0.3 mg/dL. There were fewer heart failure readmissions with rolofylline (n = 2) than with placebo (n = 7) through Day 60. Conclusions The Placebo-Controlled Study of the Effects of KW-3902 Injectable Emulsion on Heart Failure Signs and Symptoms, Diuresis, Renal Function, and Clinical Outcomes in Subjects Hospitalized with Worsening Renal Function and Heart Failure Requiring Intravenous Therapy (ie, REACH UP) study did not demonstrate any clear benefit of rolofylline in patients with ADHF and worsening renal function. However, beneficial trends raise the possibility that A 1RAs might prevent renal dysfunction in these high risk patients. To test this hypothesis, further larger studies need to evaluate the effects of adenosine A 1 antagonists in patients with progressive renal dysfunction in the face of active heart failure therapy.

Contrast induced nephropathy in patients with pre-existing renal impairment undergoing invasive coronary procedures—A long term follow up

Background: Contrast induced nephropathy (CIN) is a common complication following invasive coronary procedures. Renal dysfunction is transient in most cases. There is littledata regarding the long-termeffectsofCINonrenal function and mortality. Methods:We studied 158 patients (75%male, mean age 69± 10 years) originally enrolled in a randomised, controlled trial done at our institutions comparing Iopromide and Iodixanol in renal dysfunction patients undergoing coronary procedures. Median follow up was 40 months (range 31–49). Latest serum creatinine was obtained and difference from pre-procedure levels calculated. An absolute increase >44 mol or increase >25% from baseline was defined as persistent renal impairment.Mortality and subsequent dialysis was noted. Results: Among 158 patients, 38 (24.1%) had CIN at day 2 or 7 following their index procedure. At follow up 20/38 (52.6%) had evidence of persistent renal impairment, compared to 30/120 (25%) patients with no CIN at baseline. In multi-variate analysis, CIN at day 2 or 7 was an independent predictor of persistent renal impairment (OR3.7: 95% CI 1.7–8, p= 0.001). Age, diabetes, hypertension and contrast type were not predictive. Two CIN patients and three non-CIN patients needed dialysis. Combined death and dialysis was 23.7% in the CIN group versus 20% in the other group (p= 0.63). Conclusion: CIN after invasive coronary procedures is associated with increased risk of persistent renal dysfunction. Increased trends were noted towards the composite of death and dialysis in the CIN group but did not reach statistical significance.

Vesicostomía en la edad pediátrica. nuestra experiencia en 43 pacientes

Cutaneous vesicostomy (CV) is a choice temporary urinary diversion technique for patients with upper urinary tract (URT) dilation, secondary to vesical o infravesical disease. The objective of this study is to share our experience in children undergoing such diversion, analysing its efficacy to prevent urinary infections, improve or resolve the ureterectasia, and stabilise or improve renal function; in short the functional and morphological recovery of URT. 43 children, mean age 2.5 years (range: 1 month-14 years) with ureterohydronephrosis grade IV-V, persistent urinary infection and/or renal function impairment underwent cutaneous vesicostomy (Blocksom's technique in 36 and Lapides' procedure in the rest). Thirty subjects had neuropathic bladder (26 with secondary vesicoureteral reflux), 7 massive primary vesicoureteral reflux, and 6 posterior urethral valve. All children (100%) with neurogenic bladder (30 cases), showed improvement of ureteral-pyelic-calyceal ectasia after the diversion, and 90% improved renal function with disappearance of vesiculoureteral reflux in 65%. Augmentation cystoplasty with gut was performed in 12 patients during vesicostomy closure, using Mitrofanoff's type diversion in 5 of them. The same continent diversion with cecal appendix was used in another 7 children as the only procedure. The remaining 11 children still retain their vesicostomy. In 5 of the 7 children with primary vesicoureteral reflux, the reflux disappeared and so the vesicostomy was closed. Reflux correction during the same surgical procedure was required for the other 2 children. Of the 6 children with posterior urethral valves, 2 received a renal transplant, one is in waiting list and the rest (50%) maintain an acceptable renal function. In the first year of follow-up, 4 patients developed symptomatic urinary infection that later disappeared. The rest had occasional asymptomatic bacteriuria that required no treatment. Complications included vesical prolapse due to ostomy in 4 patients, lithiasis in 3 and stomal stenosis in 2. We consider vesicostomy to be the choice urinary diversion technique in cases of common section obstruction and/or non-obstructive ureterohydronephrosis in new-borns who do not improve with conservative treatment.

Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: Evidence-based recommendations

Idiopathic crescentic glomerulonephritis (GN) often presents with a rapid loss of renal function and pathology showing extensive crescent formation. The disease is caused by different immunopathogenetic mechanisms, pauci-immune, often antineutrophil cytoplasmic antibody (ANCA)-positive microvasculitis, antiglomerular basement membrane (GBM) antibody disease, and immune complex formation. Historical reviews reveal poor renal prognosis, even after treatment with oral steroids and cytotoxic drugs. Prognosis has improved in the last decade. In this article, evidence-based recommendations for management are presented. Because of the high risk of end-stage renal disease (ESRD), early aggressive therapy is recommended, despite weak supporting evidence. Treatment for anti-GBM antibody-induced crescentic GN should be initiated early and should include pulse methylprednisolone, a two-week course of plasmapheresis and two months of treatment with corticosteroids and cyclophosphamide (grade B and C). Treatment for pauci-immune crescentic GN should be pulse methylprednisolone, followed by oral corticosteroids and cyclophosphamide for 6 to 12 months (grade B). Recurrences can be managed similarly (grade B), along with appropriate supportive therapy. In patients who develop ESRD, successful transplantation can be performed. Diffuse endocapillary proliferative GN is classically postinfectious. It generally has a good prognosis when no crescent formation occurs. Adult patients with persistent proteinuria, hypertension, and renal function impairment need careful follow-up and management to modify progressive hemodynamic injury.

Poststreptococcal glomerulonephritis with the nephrotic range of proteinuria

In order to characterize the clinical features in poststreptococcal glomerulonephritis (PSGN) in relation to the range of proteinuria, 27 patients with PSGN were divided into 3 groups according to the amount of urinary protein excretion; Group I: with proteinuria over 3.5 g/day (n = 8), Group II: with proteinuria between 1.0 and 3.4 g/day (n = 9) and Group III: with proteinuria less than 1.0 g/day (n = 10). Bed-rest was ordered until proteinuria decreased to less than 1.0 g/day. The serum creatinine levels in Group I were significantly higher than in Group III both on admission and at discharge, although the duration of hospitalization was longer in the former than in the latter group. Furthermore, the durations of proteinuria and hypocomplementaemia were longer in the former than in the latter. In addition, the former showed a higher systolic blood pressure and a greater expanded extracellular fluid volume expressed as body weight change during hospitalization. However, none of the patients in this study demonstrated any persistent proteinuria or renal function impairment. In conclusion, bed-rest in the acute phase of PSGN might improve the short-term prognosis of PSGN.

Physiological and Biochemical Effects of Pregnancy in Uninephrectomized Rabbits

A model of mild, persistent renal impairment was produced following uninephrectomy in 6 month old female New Zealand white rabbits infected with Encephalitozoon cuniculi. The effect of three consecutive pregnancies was assessed. No difference in plasma creatinine, creatinine clearance or total protein excretion was found at 15 months of age between 5 uninephrectomized pregnant rabbits and 5 uninephrectomized virgin animals. Mean plasma urea (11.6 ± 0.4 mmol/l) was higher at 15 months of age in 5 uninephrectomized pregnant rabbits than in 5 uninephrectomized virgin animals (7.7 ± 0.7 mmol/l)(p<0.001). During pregnancy plasma urea fell in both uninephrectomized pregnant and control pregnant animals. Total urinary protein excretion increased from 0.04 ±. 01 gm/24hrs pre-pregnancy to 0.09 ±. 02 gm/24hrs during late pregnancy in uninephrectomized rabbits (p< 0.04). Mean arterial blood pressure in the 10 uninephrectomized animals increased from 81 ± 3 mmHg to 92 ± 3 mmHg at sacrifice (p = 0.022). Repetitive pre...