Epidemiology and outcome of community-acquired acute kidney injury.

AIMS: Very little data exist regarding community-acquired acute renal injury (CA-AKI). We have identified and characterized a patient cohort with CA-AKI, and documented its impact on renal function and patient mortality. METHODS: Using the database of the Medical Biochemistry Department of the Cardiff and Vale University Health Board we identified all patients with CA-AKI over a 1 month period in 2009. Follow-up biochemical and clinical data were used to determine short-term (3 months) and long-term (3 years) outcomes. Comparisons were made to a random and an age/sex matched group. RESULTS: Patients with CA-AKI were older than a non-AKI cohort (70.3 vs 57.1 years; P < 0.0001), with a 61% male predominance. 38% had pre-existing chronic kidney disease (CKD) compared with 25% in the age- and sex-matched non-CA-AKI cohort (P = 0.007). 54% of CA-AKI were admitted for inpatient care. Admission was associated with a higher incidence of complete recovery of renal function. Mortality at 3 months was 16.5%, and was related to the severity of AKI. Over the 3 years of follow-up 71% of patients with CA-AKI developed progressive CKD which was more likely following incomplete/no recovery of renal function and in the context of pre-existing CKD. Three year mortality was 45%, which was higher than that of the age/sex matched control cohort (15.7%; P < 0.0001), but was not related to the development of progressive CKD. CONCLUSIONS: CA-AKI carries significant implications in terms of both development of progressive renal disease and high long-term patient mortality.

Prevalence of risk factors for foot ulceration in a general haemodialysis population.

It is well documented that diabetic foot ulceration contributes to increased morbidity and mortality associated with renal replacement therapy. Much less is known about the risk of foot ulceration and lower limb amputation in the non-diabetic dialysis population. The aim of this study was to determine if the prevalence of risks factors for lower limb amputation in a stable haemodialysis population was greater in the diabetic cohort compared with the non-diabetic cohort. The study design is a prospective observational cohort study. Sixty patients attending a satellite haemodialysis unit in Cardiff were invited to have a comprehensive foot assessment as part of a Podiatry service review. The medical notes and hospital information system were used to identify the diabetic cohort. Patients were classified according to diabetic status (diabetic versus non-diabetic). The Renal Foot Screening Tool was developed to prospectively identify risk factors associated with foot ulceration. The assessment included peripheral neuropathy (PN), peripheral arterial disease (PAD) and foot pathology (FP). Fifty-seven patients gave informed verbal consent prior to inclusion. Risk factors for foot ulceration were recorded at baseline in the diabetic (n = 24) and non-diabetic (n = 33) groups and mortality data was revisited after a 3-year period. FP was identified in 79% of patients. Eighteen per cent of the non-diabetic patients had PN. PAD was identified in 45% of diabetic and 30% of non-diabetic patients. Forty-nine per cent of the total cohort had ≥2 of the 3 independent risk factors for foot ulceration (16/24 diabetic versus 12/33 non-diabetic). The presence of PAD and PN was predictive of mortality independent of age. The limitations of this study are its small sample size and patients were from a single satellite dialysis unit. There was a high prevalence of risk factors for foot ulceration in this population, which were not confined to the diabetic cohort. These findings suggest that non-diabetic patients on haemodialysis therapy are also at risk of developing foot ulceration. Further work on strategies to monitor and prevent FP in this high-risk cohort is needed to minimize morbidity and mortality associated with foot ulceration.

Adult day-case renal biopsy: a single-centre experience.

BACKGROUND: Despite improvements in safety seen over the last 20 years, percutaneous renal biopsy is still associated with haemorrhagic complications. Due to concerns over delayed bleeding, most nephrologists would advocate overnight observation. Recent evidence in both adult and paediatric populations suggest that in some groups, this is unnecessary. Since 1991, we have provided a day-case renal biopsy service performing 70 such procedures per year. In this study, we present a retrospective analysis of this practice. METHODS: A total of 192 patients over a consecutive 3-year period were analysed retrospectively. Patients were selected according to standardized criteria, and biopsy was performed using a modern technique (automated biopsy needles under ultrasound guidance). Complications were identified by examination of case notes and local hospital admission databases, and by telephone interview. Our pathology database was examined for sample adequacy and diagnosis. RESULTS: There were no delayed complications in the study group with 187 patients (97.4%) being discharged home on the same day. Major complications occurred in five patients (2.6%), all related to bleeding. Of these, two needed radiological intervention to achieve haemostasis. Sufficient tissue for diagnosis was achieved in 97% of cases, with a mean of 47 ± 23 glomeruli obtained per patient. Most biopsies were obtained with ≤ 2 passes (84%). CONCLUSIONS: Our findings show that in selected adult patients, renal biopsy can be performed as a day-case procedure. Given the benefits of day-case strategies in terms of patient and healthcare costs, we advocate increased utilization of this technique.

Anemia and diabetes in the absence of nephropathy.

OBJECTIVE: Patients with diabetes commonly have a greater degree of anemia for their level of renal impairment than those presenting with other causes of renal failure. To clarify the contribution and differing roles of diabetes and nephropathy in the development of anemia in diabetic patients, we examined the hematologic and hematinic parameters of diabetic patients without nephropathy. RESEARCH DESIGN AND METHODS: The study group was comprised of 62 patients with type 2 diabetes who had been followed for a median of 7 years. For the study, these patients had additional samples taken during their annual routine blood testing for the measurement of extra parameters, including serum ferritin, serum erythropoietin (Epo) levels, and the percentage of reticulocytes. These measurements were combined with the routine parameters Hb, hematocrit, HbA(1c), and glomerular filtration rate. RESULTS: In all, 8 of the 45 male patients (17.8%) and 2 of the 17 female patients (11.8%) were classified as anemic (Hb <13g/dl and <11.5g/dl, respectively). Although only a small number of the patients had anemia as defined by normal values, a retrospective analysis of individual patients over time revealed a sustained though small decrease in Hb from initial presentation. A statistically significant difference in Epo levels (P = 0.016 by Kruskal-Wallis test) was observed from the group with the lowest (Hb < or =11.5) to that with the highest (Hb > or =14.5) Hb values, with a median Epo value of 37 (interquartile range 24-42) vs. 13 (9-15) IU/l, respectively. In contrast, there was no evidence of an increased reticulocyte response to higher levels of Epo (r = 0.134 [Pearsons], P = 0.36). Reticulocyte counts ranged from 44 (38-57) to 76.5 (56-83) in the lowest and highest Hb groups, respectively. CONCLUSIONS: Although only a small number of subjects in the group were overtly anemic, all subjects had an ongoing, small but significant decrease in Hb since presentation. This study of diabetic patients without nephropathy shows an expected increase in Epo production in response to lowering levels of Hb but without the expected reticulocyte response.

The impact of an out-reach clinic on referral of patients with renal impairment.

BACKGROUND: Early diagnosis and prompt treatment of a number of renal diseases may delay renal failure, obviate the need for renal replacement therapy and reduce co-morbidity. The aim of this study was to examine the impact of out-reach renal clinics on patterns of referral of patients with renal impairment to a nephrologist. METHODS: The number of patients with renal impairment was determined as defined by serum creatinine levels >150 micromol/l in three centres within a single NHS trust over two separate 1-week periods. None of the centres studied has a local nephrologist, however one centre (hospital A) has renal out-reach clinics, another is geographically close to a renal unit (hospital B), while the third unit (hospital C) has no nephrology presence and is geographically furthest from the renal unit. In addition, retrospective as well as follow-up data on the renal function of all patients with renal impairment was collected. RESULTS: In hospital A, there was a lower proportion of patients with unreferred renal impairment than in the other two hospitals. Within the unreferred patient group there were significantly more patients whose renal function improved during the follow-up period. A considerable proportion of patients with documented deterioration in renal function remained unknown to nephrology services 6 months after initial presentation. Other than the presence of an onsite nephrology service, the only other factor found to be significantly different in those patients not referred to nephrologists was age: as in all three centres, those not referred were significantly older. CONCLUSION: Inequity of access to renal services is an important obstacle to early referral of patients with impaired renal function. Out-reach renal services provide a model which significantly improves referral patterns.

The quest for a model of type II diabetes with nephropathy: the Goto Kakizaki rat.

The Goto Kakakizaki (GK) rat is a moderately diabetic rat strain that was developed by repeated inbreeding of glucose-intolerant Wistar rats over several generations. In contrast to many other rodent models of non-insulin-dependent diabetes, GK rats do not exhibit hyperlipidemia or obesity. Hyperglycemia in the GK rat is associated with the development of age-dependent renal structural changes that are similar to those described in patients with prolonged non-insulin-dependent diabetes mellitus who have not developed overt renal disease. Hyperglycemia in the GK rat is, however, not associated with overt proteinuria or progressive nephropathy. In the present review the metabolic characteristics as well as renal and nonrenal changes observed in GK rats are described. Moreover the effects on renal function and morphology of secondary injurious stimuli, such as mesangioproliferative glomerulonephritis and hypertension, superimposed on type II diabetes in GK rats are discussed.

Glucose modulates handling of apoptotic cells by mesangial cells: involvement of TGF-beta1.

Glucose stimulates proapoptotic signalling pathways in mesangial cells. Studies focused on inflammatory glomerular injury have demonstrated that removal of apoptotic mesangial cells occurs by neighbouring non-apoptotic mesangial cells. The aim of this study was to define the effect of ambient glucose concentration on mesangial handling of apoptotic cells, and in addition to examine the response made by the mesangial cell. We used a co-culture model in which neutrophils aged overnight to induce apoptosis, or apoptotic mesangial cells, labelled with a fluorescent dye, were added to mesangial cells to study phagocytosis. Exposure of mesangial cells to an ambient glucose concentration of 25 mM D-glucose before addition of apoptotic cells led in an increase in mesangial cell phagocytosis. Ingestion of apoptotic cells was inhibited by blocking alpha v beta 3 integrin-vitronectin receptor or thrombospondin-1. Furthermore, glucose-dependent stimulation of phagocytosis was inhibited by a blocking antibody to TGF-beta1. Co-culture of apoptotic cells with mesangial cells stimulated synthesis of TGF-beta1 as compared to freshly isolated neutrophils. Increased TGF-beta1 synthesis was dependent on direct contact between the two cell types but was not dependent on phagocytosis of apoptotic cells, as TGF-beta1 generation was not affected by inhibition of the thrombospondin-1 pathway. We propose a model in which apoptotic cell binding but not phagocytosis stimulates enhanced mesangial cell TGF-beta1 synthesis. Furthermore phagocytosis, which involves the thrombospondin-1 pathway, is uncoupled from binding of apoptotic cells, which stimulated TGF-beta1 synthesis.

Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy.

BACKGROUND: Type II diabetes in the Goto Kakizaki (GK) rats (derived from Wistar rats) is not associated with the development of obesity, hyperlipidemia, hypertension, or pronounced renal functional changes. The aim of this study was to investigate the effect of superimposed hypertension on renal function and morphology under conditions of hyper- and normoglycemia. METHODS: The evolution of biochemical and morphologic renal changes was examined in GK and Wistar rats treated with deoxycorticosterone acetate (DOCA) salt over 24 weeks. RESULTS: Blood pressure was increased from 6 weeks on in GK and Wistar rats with no difference in blood pressure levels between both groups (week 24, 183 +/- 14 mm Hg vs. 191 +/- 13 mm Hg, P = NS, vs. 144 +/- 6 mm Hg in normal controls, P < 0.01). A progressive increase in proteinuria was observed in hypertensive GK rats from 12 weeks on (week 24, 168 +/- 62 mg/day vs. 41 +/- 30 mg/day in hypertensive Wistar rats, P = 0.002). Histologic analysis at weeks 15 and 24 showed progressive glomerulosclerosis in hypertensive GK and Wistar rats (week 24, 13 +/- 4% vs. 8 +/- 1%, P = NS) but not in nonhypertensive GK controls. This was associated with evidence of podocyte damage (de novo desmin expression) in hypertensive as compared to nonhypertensive GK rats (week 24, score 1.4 +/- 0.1 vs. 0.8 +/- 0.1, P < 0.001) while no significant increase was observed in hypertensive vs. nonhypertensive Wistar rats. Tubulointerstitial damage was increased in hypertensive GK as compared to hypertensive Wistar rats (week 24, score 1.5 +/- 0.6 vs. 0.6 +/- 0.3, P = 0.01). By immunohistochemistry, this was associated with an up-regulation of tubulointerstitial type IV collagen as well as alpha-smooth muscle actin (alpha-SMA) expression, macrophage infiltration and cell proliferation in hypertensive GK rats. CONCLUSION: Our data demonstrate that long-standing type II diabetes alone is not sufficient to induce progressive nephropathy unless secondary injurious mechanisms such as hypertension are present. The hypertensive GK rat provides a novel model to investigate the mechanisms involved in diabetic nephropathy.