Intrinsic Renal Damage Research Articles

#1230 Comparative analysis of vitamin D status between patients with advanced chronic kidney disease and those on dialysis

Abstract Background and Aims Decreased plasma concentration of 1,25-dihydroxy-vitamin D3 or calcitriol, the most active biological form of vitamin D3, in patients with advanced chronic kidney disease (ACKD) and on dialysis, is almost universal. In addition, 25-50% of these patients also have decreased levels of 25-hydroxy-vitamin D3 (calcidiol or calcifediol). The main cause of calcitriol deficiency is decreased hydroxylation in the kidney, both due to intrinsic renal damage and hyperphosphataemia. Calcifediol deficiency is directly related to decreased intake and sun exposure. We already know that this calcifediol deficiency is associated with ACKD, but we do not know if there are differences between ACKD patients and dialysis patients. The aim of this study is to analyse whether there are differences in calcifediol levels between ACKD and dialysis patients. Method An observational, analytical, ambispective, multicentre, analytical study was carried out with the participation of five Centres in Spain, under conditions of routine clinical practice. As study subjects, we included patients with ACKD and on haemodialysis from the University Hospitals of Virgen del Rocío, La Paz and Nuestra Señora de Candelaria, and the dialysis centres: Avericum, Quironsalud Tenerife. We selected demographic variables and also included serum levels of calcifediol, calcium, phosphorus and PTH; treatment with: phosphorus binders, erythropoietin synthesis analogues (ESA), ferrotherapy, calcimimetics, active vitamin D, native vitamin D. Data are organised and analysed with SPSS Statistics v22. In all analyses, the significance level is set for a P value < 0.05. Multivariate logistic regression analysis was also performed. Results A total of 161 patients were included. Both groups were homogeneous in the presence of diabetes, calcium levels and treatment with iron, native vitamin D, active vitamin D and calcimimetics. There were significant differences in sex, age, phosphorus levels, PTH, phosphate binders, ESA treatment. There are no significant differences in calcifediol levels or vitamin D status between the two comparison groups. Conclusion In our study, within a general context of hypovitaminosis D, patients with ACKD have a vitamin D status similar to dialysis patients.

Kidney injury molecule-1 and urinary gamma-glutamyl transferase as biomarkers of acute kidney injury in cats.

To evaluate the concentration of kidney injury molecule-1 and activity of urinary gamma-glutamyl transferase in cats with urethral obstruction and healthy cats. Blood and urine samples were collected from a group of 15 healthy cats (control group) and a group of 20 cats with urethral obstruction at presentation, and 24hours and 7 days after unblocking the obstruction. The serum creatinine, urinary creatinine and urinary gamma-glutamyl transferase were measured by spectrophotometry and kidney injury molecule-1 by the sandwich enzyme-linked immunosorbent assay. On presentation, cats with obstruction had serum creatinine concentration and urinary gamma-glutamyl transferase index higher than healthy cats (mean difference 544 μmol/L, 95% confidence intervals 222 to 865 μmol/L, and 0.0022 U/μmol-uCre, 0.00043 to 0.0039 U/μmol-uCre, respectively), urine creatinine concentration lower (mean difference 25,624 µmol/L, 17,329 to 33,919 µmol/L), and no significant difference in the kidney injury molecule-1/urinary creatinine ratio (mean difference 13 pg/μmol-uCre, -33 to 59 pg/μmol-uCre). In the group of cats with urinary obstruction, over time serum creatinine decreased, urine creatinine increased, urinary gamma-glutamyl transferase index did not change significantly, and kidney injury molecule-1/urinary creatinine ratio increased. Cats with post-renal obstruction and potential intrinsic renal damage had higher urinary gamma-glutamyl transferase index than healthy cats at the time of presentation and showed increase in kidney injury molecule-1/urinary creatinine ratio over time.

Sodium Intake Is Associated With Renal Resistive Index in an Adult Population-Based Study

Renal resistive index (RRI) has been associated with adverse renal and cardiovascular outcomes. Although traditionally considered a marker of intrinsic renal damage, RRI could also reflect systemic vascular dysfunction. As sodium intake was linked to alterations in vascular properties, we wished to characterize the association of salt consumption with RRI in the general adult population. Participants were recruited in a population-based study in Switzerland. RRI was measured by ultrasound in 3 segmental arteries. Sodium intake (UNa; mmol/24 h) was estimated on 24-hour urine samples. Carotido-femoral pulse wave velocity was obtained by applanation tonometry. Mixed multivariate regression models were used with RRI or pulse wave velocity as independent variables and UNa as dependent variable, adjusting for possible confounders. We included 1002 patients in the analyses with 528 (52.7%) women and mean age of 47.2±17.4. Mean values of UNa and RRI were 141.8±61.1 mmol/24 h and 63.8±5.5%, respectively. In multivariate analysis, UNa was positively associated with RRI (P=0.002) but not with pulse wave velocity (P=0.344). Plasma renin activity and aldosterone did not modify the relationship between UNa and RRI (P=0.087 for interaction). UNa/urinary potassium ratio was positively associated with pulse wave velocity ≥12 m/s (P=0.033). Our results suggest that dietary salt consumption has a direct impact on renal hemodynamic in the adult general population. Alterations in vascular properties likely explain those findings, but inadequate renal vaso-motor response is also possible. Sodium intake could thus potentially be linked to underlying structural systemic damages affecting this population.

Clinical and laboratory predictors of Lassa fever outcome in a dedicated treatment facility in Nigeria: a retrospective, observational cohort study

Lassa fever is a viral haemorrhagic disease endemic to west Africa. No large-scale studies exist from Nigeria, where the Lassa virus (LASV) is most diverse. LASV diversity, coupled with host genetic and environmental factors, might cause differences in disease pathophysiology. Small-scale studies in Nigeria suggest that acute kidney injury is an important clinical feature and might be a determinant of survival. We aimed to establish the demographic, clinical, and laboratory factors associated with mortality in Nigerian patients with Lassa fever, and hypothesised that LASV was the direct cause of intrinsic renal damage for a subset of the patients with Lassa fever. We did a retrospective, observational cohort study of consecutive patients in Nigeria with Lassa fever, who tested positive for LASV with RT-PCR, and were treated in Irrua Specialist Teaching Hospital. We did univariate and multivariate statistical analyses, including logistic regression, of all demographic, clinical, and laboratory variables available at presentation to identify the factors associated with patient mortality. Of 291 patients treated in Irrua Specialist Teaching Hospital between Jan 3, 2011, and Dec 11, 2015, 284 (98%) had known outcomes (died or survived) and seven (2%) were discharged against medical advice. Overall case-fatality rate was 24% (68 of 284 patients), with a 1·4 times increase in mortality risk for each 10 years of age (p=0·00017), reaching 39% (22 of 57) for patients older than 50 years. Of 284 patients, 81 (28%) had acute kidney injury and 104 (37%) had CNS manifestations and thus both were considered important complications of acute Lassa fever in Nigeria. Acute kidney injury was strongly associated with poor outcome (case-fatality rate of 60% [49 of 81 patients]; odds ratio [OR] 15, p<0·00001). Compared with patients without acute kidney injury, those with acute kidney injury had higher incidence of proteinuria (32 [82%] of 39 patients) and haematuria (29 [76%] of 38) and higher mean serum potassium (4·63 [SD 1·04] mmol/L) and lower blood urea nitrogen to creatinine ratio (8·6 for patients without clinical history of fluid loss), suggesting intrinsic renal damage. Normalisation of creatinine concentration was associated with recovery. Elevated serum creatinine (OR 1·3; p=0·046), aspartate aminotransferase (OR 1·5; p=0·075), and potassium (OR 3·6; p=0·0024) were independent predictors of death. Our study presents detailed clinical and laboratory data for Nigerian patients with Lassa fever and provides strong evidence for intrinsic renal dysfunction in acute Lassa fever. Early recognition and treatment of acute kidney injury might significantly reduce mortality. German Research Foundation, German Center for Infection Research, Howard Hughes Medical Institute, US National Institutes of Health, and World Bank.

Histological and biochemical changes induced by ethanolic leaf extract of Moringa oleifera in the heart and kidneys of adult wistar rats

Study Background: Moringa oleifera, (miracle tree), has been used in the treatment of numerous diseases. Moringa has been the subject of intensive scientific research; however, there have been scanty information on its sub-acute effect on the kidneys. Aims: This work was done to investigate the histological and biochemical effect of M. oleifera on the heart and kidneys of adult Wistar rats. Settings and Design: Twenty-eight adult healthy rats were used for this study. The rats were divided into 4 groups of 7 per group and fed with pellets and water ad libitum. Group A served as the control, Group B were fed with 500 mg/kg of ethanolic extract of Moringa leaf, Group C with 1000 mg/kg while Group D were fed with 1500 mg/kg body weight. Methods and Material: Doses were administered once daily using oral gavage for 28 days. Before the time of sacrificing the animals, blood samples were collected into plain test tubes and the animals anesthetized before sacrifice. Necropsy was performed and the tissues (heart and kidney) processed and stained using Hematoxylin and Eosin staining techniques. Serum electrolyte (sodium and potassium), urea, creatinine, creatine kinase, and lactate dehydrogenase were analyzed for. Results: There were significant increases in urea and potassium in the 1000 mg/kg (41.26 ± 16.89 and 10.52 ± 1.48) and 1500 mg/kg (44.23 ± 17.49 and 13.82 ± 1.57) treated animals when compared with the control (21.47 ± 16.33 and 4.54 ± 1.09). Histo-architecture of the kidneys showed glomerula atrophy in the 1000 mg/kg and 1500 mg/kg treated rats which is indicative of intrinsic renal damage. There were no noticeable structural damage on the heart. Conclusions: The result showed that M. oleifera may be toxic to the kidneys at concentrations higher than 1000 mg/kg.

Acute Renal Failure in the Neonate.

Acute renal failure (ARF) is a common disorder in high-risk neonates. ARF may be oliguric or nonoliguric, the latter having a better prognosis. Risk factors for ARF include prematurity, respiratory and vascular disorders, heart failure, congenital uropathies, and the use of nephrotoxic drugs. Chemical analysis of urine and ultrasounds help differentiate the nature and the type of ARF: prerenal, intrinsic, or postrenal. Conservative management of prerenal forms of ARF consists in carefully restoring cardiac output and controlling fluid and electrolyte balances. Early relief of obstruction is mandatory in severe postrenal forms of ARF. Renal replacement therapy is often necessary when ARF is secondary to intrinsic renal damage: peritoneal dialysis is the treatment of choice. Hemodialysis and continuous venovenous hemofiltration may be used in specific cases. Overall prognosis of ARF depends on the nature and severity of the renal injury that has led to renal failure.

Optimal Medical Management in Patients with Renovascular Hypertension

Renovascular hypertension refers to the rise of arterial pressure due to reduced perfusion of the kidney caused by the stenotic renal artery/ies. The most common cause of stenotic renal artery is atherosclerosis. Atherosclerotic renal stenosis is usually part of a systemic syndrome that involves hypertension, intrinsic renal damage, and cardiovascular morbidity. So far, large trials have not proven the superiority of interventional therapies to medical management. As a result, renal artery stenosis should be treated mainly as a coronary artery disease equivalent focusing on rigorous management of hypertension, hyperglycemia, and hyperlipidemia. Antihypertensive treatment should include renin-angiotensin system blockade medication in most cases, while HMG-CoA reductase inhibitors (statins) can be used even in chronic kidney disease with safety. Lifestyle modifications, such as cessation of smoking, and antiplatelet therapy have reduced the risk of cardiovascular events in high-risk patients.

Anticancer Drug???Induced Kidney Disorders

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium thiosulfate and diethyldithiocarbamate. Dose- and age-related proximal tubular damage is an adverse effect of ifosfamide. In addition to renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have occurred with ifosfamide treatment. High dose azacitidine causes renal dysfunction manifested by tubular acidosis, polyuria and increased urinary excretion of electrolytes, glucose and amino acids. Haemolytic uraemia is a rare adverse effect of gemcitabine. Methotrexate can cause increased serum creatinine levels, uraemia and haematuria. Acute renal failure is reported following administration of high dose methotrexate. Urinary alkalisation and hydration confer protection against methotrexate-induced renal dysfunction. Dose-related nephrotoxicity, including acute renal failure, are reported subsequent to treatment with pentostatin and diaziquone. Acute renal failure is a rare adverse effect of treatment with interferon-alpha. Haemolytic uraemic syndrome occurs with mitomycin administration. A mortality rate of 50 to 100% is reported in patients developing mitomycin-induced haemolytic uraemic syndrome. Capillary leak syndrome occurring with aldesleukin therapy can cause renal dysfunction. Infusion-related hypotension during infusion of high dose carmustine can precipitate renal dysfunction.

A clinicopathological study of 90 children with acute renal failure

Clinical presentation, laboratory findings, renal biopsy findings and subsequent clinical course were studied retrospectively in 90 children with acute renal failure to intrinsic renal damage. The mean age at presentation was 8.1 years. Diagnosis and number of patients were as follows: Hemolytic uremic syndrome (HUS) in 32 patients, tubulo-interstitial nephritis in 19, idiopathic nephrotic syndrome in 10, IgA nephropathy on 9, membranoproliferative glomerulonephritis in 8, lupus in 5, poststreptococcal glomerulonephritis in 4, cortical necrosis in 1, Henoch Schoenlein purpura nephritis in 1 and anti-neutrophil cytoplasmic antibody associated glomerulonephritis in 1. Thirty-nine patients needed dialysis, but 36 of these were able to stop dialysis, 3 patients with HUS without gastrointestinal symptoms needed chronic dialysis. The mean follow-up period was 7.3 years from onset, and the the latest follow-up 82 patients had normal renal function, 3 showed chronic renal failure, 2 had regular dialysis, 2 had successful renal transplantation, an 1 had died due to heart failure. A poor outcome was associated with diffuse crescents and the presence of severe vascular changes. The early biopsy findings were very useful for the management of children with acute renal failure.

Acute Renal Failure

In recent years, no aspect of clinical nephrology has expanded with as much new information as the broad subject of acute renal failure. This clinical syndrome of diverse etiologies is characterized by acute deterioration of renal function. It may occur not only as a result of intrinsic renal damage, but also from impairment of renal perfusion or with urinary tract obstruction. The clinical spectrum of acute renal failure is constantly changing with new advances in clinical practice, such as the use of different antibiotics or more modern methods of diagnostic imaging. The clinician must keep abreast not only of pathophysiology, but also of new etiologies and various methods for correction of metabolic abnormalities with nutritional therapy and dialysis. This edition of<i>Acute Renal Failure</i>is a comprehensive but readable text about this most common syndrome encountered in the subspecialty of nephrology. This hardcover book is organized into five sections: pathophysiology,

Host factors in the pathogenesis of urinary tract infections

Classic animal studies conducted two decades ago provided the basic understanding of the pathogenesis of urinary tract infections. Those studies emphasized the natural resistance of the urinary tract to colonization and infection. Urinary obstruction, stasis, and reflux remain of great importance in all age groups in predisposing to infection. Recent studies of the crucial role of bacterial adherence to epithelial cells lining the genitourinary tract have shed new light on the pathogenesis of urinary infection. Information from adherence studies may have considerable clinical relevance with regard to the development of vaccines that prevent bacterial invasion particularly in the upper urinary tract. The normal defense mechanisms present in the human urinary tract are discussed. Despite progress in our understanding of the pathogenesis of urinary infection, considerable controversy still exists particularly with regard to host susceptibility to recurrent lower urinary tract infections in women with anatomically normal urinary tracts. Recent studies also have emphasized the significance of the host's normal immunologic mechanisms in contributing to intrinsic renal damage after upper urinary tract invasion by bacteria.

Long-term patient and renal prognosis in acute renal failure.

A long-term clinicomorphological study in 227 patients with acute renal failure due to intrinsic renal damage shows the clinical value of renal biopsy for assessing treatment and predicting prognosis. Early morphological diagnosis enables appropriate therapeutic measures, which play their part in patient survival and renal survival. Present long-term results show that 5 years after the acute episode, chronic renal failure may be expected to occur in about 50% of cases with acute renal failure due to glomerular and vascular injuries. Tubulointerstitial lesions are associated with definitely better long-term prognosis.

Acute Renal Failure in Cardiovascular and Other Surgical Patients

The acute onset of oliguria and azotemia in the postoperative setting may be caused by prerenal or postrenal causes or intrinsic renal damage. The first step in arriving at a diagnosis is to review the history in order to elicit the extrarenal factors. Certain simple laboratory tests are of tremendous value in differentiating these conditions. The development of acute renal failure with renal parenchymal damage usually occurs in the setting of hypotension, sepsis, dehydration, and with exposure to nephrotoxins. Most patients will be excreting scant amounts of isotonic urine containing more than 20 to 30 mEq per liter of sodium. Their urine:plasma creatinine ratio is less than or equal to 20:1 and their urinary sediment reveals many epithelial cells and casts. The condition is usually reversible and the treatment is expectant. However, it is still associated with a high mortality, although the survival of patients with acute renal failure may be substantially higher than previously reported. Early dialysis and nutritional support may play an important role in the improved survival. Patients with nonoliguric acute renal failure have urine outputs that may exceed 2 liters per day. Despite this output they demonstrate a stepwise increase in serum urea and creatinine. Urine sodium and osmolality are not very helpful. Many such patients do have low (less than 20 mEq per liter) urine sodium concentration and excrete isotonic urine.

Pre- and Postoperative Renal Failure

The acute onset of oliguria and azotemia in the postoperative setting may be caused by pre-renal causes or intrinsic renal damage. The first step in arriving at a diagnosis is to review the history as noted above for clues regarding fluid balance, treatment with nephrotoxins, etc. The typical patient with prerenal azotemia will present with evidence of the recent onset of worsening of pre-existing cardiac disease, renal or gastrointestinal fluid loss, or the accumulation of acites, edema, or retroperitoneal fluid. In the absence of very recent diuretic therapy, he will be excreting a scant amount of concentrated (greater than 400 mOsm per L) sodium free (less than 10 to 20 mEq per L) urine. The serumBUN/Cr ratio is often greater than 15 to 20:1, and their urinary sediment will be bland. In an occasional patient in whom these studies give equivocal results, additional help may be obtained with measurements of central venous pressure (CVP) or pulmonary wedge pressure (PWP) and by noting their response to intravenous fluid loading. A rising CVP or PWP in the face of salt loading is, of course, evidence against prerenal azotemia. Patients with obstructive uropathies may be oligoanuric or polyuric-occasionally a characteristic alternating polyuria and oliguria is found (due to displacement of a stone or relief of edema). When oliguric their urine typically contains substantial amounts of sodium (greater than 20 mEq per L), is isotonic, and their OsmU:OsmP is les s than or equal to 1.2. Their urinary sediment will reflect the cause of their obstruction as noted above. A renal scan, ultrasound study, or infusion IVP are mandatory to rule out the possibility of obstructive uropathy. If these nonivasive studies are equivocal, one must consider doing a unilateral retrograde. The development of ATN usually occurs in the setting of hypotension, sepsis, dehydration, and with exposure to nephrotoxins. Most patients with be excreting scant amounts of isotonic urine containing more than 20 to 30 mEq per L of sodium. Their CrU:CrP is less than or equal to 20:1 and their urinary sediment reveals many epithelial cells and casts. Those patients with nonoliguric ATN have urine outputs which may exceed 2 liters per day. Despite this output they demonstrate a stepwise increase in serum urea and creatinine. Urine sodium and osmolality are not very helpful in this setting. Many such patients do have low (less than 20 mEg per L) urine sodium concentration and excrete isotonic urine.

Cross-circulation study of natriuretic factors in postobstructive diuresis.

To study the role of circulating natriuretic factors in the postobstructive diuresis that occurs after relief of bilateral, but not unilateral ureteral ligation, cross-circulation was carried out between normal recipient rats and donor rats have either 24-h bilateral (BUL) or unilateral (UUL) ureteral ligation. With BUL donors, there was a rapid marked increase in sodium and water excretion in the recipient rats, sustained for 80-140 min, with a peak approximately 10 times control values. With UUL donors, no significant natriuretic response occurred. Changes in glomerular filtration rate, renal plasma flow, blood pressure, hematocrit, or circulating levels of aldosterone or Pitressin did not explain the diuresis-natriuresis produced by cross-circulation with BUL donors. Differences in the intrinsic renal damage produced by bilateral as compared to unilateral ureteral obstruction did not appear to account for this response, since UUL donors given an acute urea load and urine reinfusion caused a similar diuresis-natriuresis. Moreover, normal donor rats given a urea load also caused a diuresis-natriuresis nearly equal to that produced by BUL rats, and the relationship between increased urea excretion and sodium excretion or urine flow in the recipients was not different in the two groups. Total urine reinfusion for 3 h in donor rats produced a significant, although less marked, diuresis-natriuresis in recipient animals, with only a slight elevation of the blood urea nitrogen level, much less increase in urea excretion rate, and no significant relationship between urea excretion and sodium excretion or urine flow. The results indicate that potent natriuretic factors, which act by decreasing the tubular reabsorption of sodium and water, are present in the blood of rats with bilateral, but not unilateral, ureteral ligation. High blood and urine urea levels appear to be the factors responsible for the marked natriuresis-diuresis occurring in normal rats during cross-circulation with BUL donors, although suggestive evidence of other natriuretic factors in urine reinfused intravenously was also obtained. The data suggest that urea osmotic diuresis is an important mechanism for determining the striking difference between the postobstructive diuresis observed after relief of bilateral as compared to unilateral ureteral ligation.