Urine macrophages reflect kidney macrophage content during acute tubular interstitial and glomerular injury.

Macrophage polarization is a major contributing factor in acute kidney injury (AKI). We aim to determine its biomarker value in differentiating etiologic causes of various intrinsic renal AKI. A total of 205 patients with renal intrinsic AKI were enrolled. Urinary sCD163 was quantified and macrophage subtypes in urine and in renal biopsy were determined. Compared to healthy controls and AKI due to interstitial or tubular injuries (0 pg/µmol), urinary sCD163 was markedly higher in glomerulopathy, especially in diffuse proliferative glomerulonephritis (275.5 pg/µmol) and significantly correlated with cellular crescent formation. Urine sediment analysis of M1/M2 ratio could differentiate acute tubulointerstitial nephritis (M1/M2 > 2.35) from crescentic glomerulonephritis (M1/M2 < 0.27). Urinary sCD163 levels and M2 subtype positively correlated with infiltrated M2 in the glomeruli, whereas urine M1 positively correlated with infiltrated M1 in the interstitium. Of note, urinary sCD163 showed better diagnositic performance in differentiating disease etiologies compared to tradiational urinary biomarkers of AKI (NGAL and KIM-1) and markers of myeloid cells (CD11b) and pan macrophages (CD68). Thus markers of macrophage polarization could be viewed as the noninvasive "liquid biopsy" in the presence of various intrinsic kidney diseases.

Assessment and prediction of acute kidney injury in patients with decompensated cirrhosis with serum cystatin C and urine N-acetyl-ß-D-glucosaminidase.

BACKGROUND AND AIM: For appropriate management of acute kidney injury (AKI) in cirrhotic patients, accurate differentiation of the types of AKI, prerenal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN) is very important. Urine N-acetyl-ß-D-glucosaminidase (NAG) has been proposed as a good tubular injury marker in many studies, but its efficacy in cirrhosis is unclear. This study was performed to evaluate the usefulness of urine NAG in patients with decompensated cirrhosis. METHODS: In 114 hospitalized patients with decompensated cirrhosis, we assessed serum creatinine, cystatin C, and urine NAG levels as markers for AKI differentiation and development and patient mortality. RESULTS: Thirty patients diagnosed with AKI at baseline had significantly higher serum creatinine and cystatin C levels, urine NAG levels, and Child-Pugh scores than those without AKI. Only urine NAG levels were significantly higher in patients with ATN than those with PRA or HRS (116.1 ± 46.8 U/g vs 39.4 ± 20.2 or 54.0 ± 19.2 U/g urinary creatinine, all P < 0.05). During a median follow up of 6.1 months, AKI developed in 17 of 84 patients: PRA in nine, HRS in six, and ATN in three. Higher serum cystatin C and urine NAG levels were independent predictors of AKI development in patients with decompensated cirrhosis. Survival was significantly associated with low serum cystatin C and urine NAG levels. CONCLUSION: Serum cystatin C and urine NAG levels are useful to differentiate types of AKI and are strong predictors for AKI development and mortality in patients with decompensated cirrhosis.

Overexpression of Intrarenal Renin-Angiotensin System in Human Acute Tubular Necrosis.

BACKGROUND/AIMS: Acute tubular necrosis (ATN), a leading cause of acute kidney injury (AKI), is associated with decreased survival and increased progression of chronic kidney disease. A barrier to improving the clinical outcomes is the incomplete understanding of the pathogenesis of AKI. Our objective is to test the hypothesis that intrarenal renin-angiotensin system (RAS) is overexpressed in patients with ATN and could be an indicator of ATN severity. METHODS: A transversal study was conducted in patients with biopsy-proven ATN. Intrarenal expression of angiotensinogen and angiotensin II, and urinary angiotensinogen were measured. RESULTS: Patients with ATN demonstrated upregulation of intrarenal RAS, evidenced by upregulation of intrarenal angiotensinogen and angiotensin II. Patients with ATN also have elevated urinary angiotensinogen level that correlated with the overexpressed intrarenal RAS. Moreover, this increase in intrarenal RAS expression and urinary angiotensinogen was associated with the extent of acute tubular injury and urinary albumin excretion, respectively. CONCLUSIONS: We demonstrate that the intrarenal RAS is upregulated in patients with ATN and is associated with the severity of ATN. Urinary angiotensinogen reflects intrarenal RAS status, and is of value to assess the severity of ATN.

Urinary liver-type fatty acid-binding protein predicts recovery from acute kidney injury.

OBJECTIVES: Despite significant advances in the epidemiology of acute kidney injury (AKI), there is no reliable method to predict renal recovery. Using acute kidney injury network (AKIN) criteria, we tested whether higher urinary L-FABP (uL-FABP) concentrations in the patients with AKIN stage 3 (AKIN3) after nephrology consultation would predict failure to recover. METHODS: This is a prospective cohort study of 114 patients with AKIN3 at WuXi People's Hospital from August 2011 to July 2014. The levels of serum creatinine, urine creatinine, and uL-FABP were obtained at the time of nephrology consultation. RESULTS: Patients who recovered had lower uL-FABP than those who failed to recover at time of nephrology consultation (71.42 (11.1 - 118.3) vs. 335.18 (103.9 - 422.3) ng/mg × creatinine, p < 0.001). Urinary L-FABP predicted failure to recover with an area under the receiver operating characteristic curve of 0.906 (95% CI 0.837 - 0.953). A clinical model using age, APACHE II score and acute tubular necrosis severity scoring index (ATN-ISS) predicted failure to recover with an area under the curve of 0.825 (95% CI 0.743 - 0.890). When uL-FABP was compared to the clinical model, the reclassification of risk of renal recovery had significantly improved by 35.1%. CONCLUSION: Urinary L-FABP appears to be a useful biomarker to predict failure to recover during hospitalization in the cohort of patients with AKIN3.

Urinary Kidney injury molecule-1 can predict delayed graft function in living donor renal allograft recipients.

AIM: Delayed graft function is an early complication leading to impaired creatinine clearance, urine formation and determinant of long term graft outcome. The aim of the present study was to determine the earliest predictive cut-off value of uKIM-1 level in patients with delayed graft function and acute tubular necrosis. METHODS: We have determined the serial urinary KIM-1 normalized to urinary creatinine (uKIM-1, pg/mg) level at 0, 6, 12, 18, 24 and 48 h of post-transplant by ELISA methods. RESULT: The normalized uKIM-1 and AUC-ROC, of uKIM-1 were progressively increased up to 48 h in both delayed graft function (DGF) and immediate graft function (IGF). The u KIM-1 values were significantly high at 6, 12, 18, 24 and 48 h in patients with DGF as compared to that of IGF except at half an hour post-transplant values. Although, progressive increase in uKIM-1 values were observed in both groups of patients; there was an overlap of values between two groups up to 12 h. The earliest non-overlapping values of uKIM-1 between the groups were observed at 18 h onwards and minimum difference of 923.43 pg/mg. The earliest predictive AUC-ROC of uKIM-1 in patients with DGF without overlap with IGF was also observed at 18 h post-transplant with specificity of 100% and sensitivity of 89.9%. CONCLUSION: Serial uKIM-1 measurement can be used as non-invasive diagnostic biomarkers to predict the incident of DGF in living donor renal transplant recipients. At 18(th) post-transplant hour uKIM-1 can predict DGF with 100% specificity and 89.9% sensitivity with a cut-off value of normalized KIM-1 of 923.43 pg/mg.

Acute renal failure in cirrhotic patients with severe sepsis: value of urinary interleukin-18.

BACKGROUND AND AIM: Acute renal failure (ARF) is a common complication of liver cirrhosis and severe sepsis. Differentiating functional renal failure from acute tubular necrosis (ATN) has been difficult in this clinical setting. It has been shown that urinary interleukin 18 (IL-18) can serve as a sensitive marker for ARF and ATN. This study was aimed to investigate the diagnostic and prognostic values of urinary IL-18 in ARF associated with liver cirrhosis and severe sepsis. METHODS: We prospectively evaluated the relationship between urinary IL-18 and clinical outcomes in 168 consecutive cirrhotic patients with severe sepsis. RESULTS: One hundred and eight patients (64.3%) developed ARF at admission to the intensive care unit. ARF was associated with higher urinary IL-18 and impaired effective arterial volume. Renal failure was functional in 64 (59.2%), due to acute tubular necrosis (ATN) in 30 (27.7%), and mixed type in 14 (12.9%). Patients with ATN had significantly higher levels of urinary IL-18, rates of vasopressor dependency, and hospital mortality than those with functional renal failure. By using the areas under receiver operating characteristic (AUROC) curve, urinary IL-18 demonstrated an excellent discriminative power (AUROC 0.882) for diagnosing tubular injury in those with ARF. Meanwhile, hospital survivors had significantly lower urinary and serum IL-18 levels, compared to non-survivors. In multivariate analysis, urinary IL-18, international normalized ratio, and mean arterial pressure were independent factors to predict hospital mortality. CONCLUSIONS: Urinary IL-18 can serve as a diagnostic and prognostic marker in cirrhotic patients with severe sepsis.

Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis.

BACKGROUND & AIMS: Impairment of kidney function is common in cirrhosis but differential diagnosis remains a challenge. We aimed at assessing the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of tubular damage, in the differential diagnosis of impairment of kidney function in cirrhosis. METHODS: Two-hundred and forty-one patients with cirrhosis, 72 without ascites, 85 with ascites, and 84 with impaired kidney function, were studied. Urinary levels of NGAL were measured by ELISA. RESULTS: Patients with impaired kidney function had higher urinary NGAL levels compared to patients with and without ascites. Patients with urinary tract infection (n=25) had higher uNGAL values than non-infected patients. Patients with acute tubular necrosis (ATN) had uNGAL levels markedly higher (417µg/g creatinine (239-2242) median and IQ range) compared to those of patients with pre-renal azotemia due to volume depletion 30 (20-59), chronic kidney disease (CKD) 82 (34-152), and hepatorenal syndrome (HRS) 76 (43-263) µg/g creatinine (p<0.001 for all). Among HRS patients, the highest values were found in HRS-associated with infections, followed by classical (non-associated with active infections) type-1 and type-2 HRS (391 (72-523), 147 (83-263), and 43 (31-74) µg/g creatinine, respectively; p<0.001). Differences in uNGAL levels between classical type 1 HRS and ATN on the one hand and classical type 1 HRS and CKD and pre-renal azotemia on the other were statistically significant (p<0.05). CONCLUSIONS: uNGAL levels may be useful in the differential diagnosis of impairment of kidney function in cirrhosis. Urinary tract infections should be ruled out because they may increase uNGAL excretion.

Urinary kidney injury molecule-1 in patients with IgA nephropathy is closely associated with disease severity.

BACKGROUND: The pathological characteristics of IgA nephropathy (IgAN) are highly variable. Urinary kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubule injury. The aim of the study is to investigate the value of KIM-1 as a biomarker for assessing the renal injury in IgAN. METHODS: The levels of urinary KIM-1 in 202 patients with IgAN, 46 patients with other renal diseases as disease controls and 60 healthy blood donors as normal controls were measured. Correlations with clinical and histopathological features of patients with IgAN were evaluated. RESULTS: The levels of urinary KIM-1 were significantly higher in patients with IgAN than in normal controls (P < 0.001) and in patients with non-IgAN (P = 0.011). Urinary levels of KIM-1 in IgAN positively correlated with levels of serum creatinine and proteinuria and negatively with creatinine clearance. The more severe the tubulointerstitial injury was, the higher the levels of urinary KIM-1. Patients with severe mesangial proliferation, crescents formation or endocapillary proliferation had higher levels of urinary KIM-1 than those without. The levels of tubular KIM-1 expression in immunohistochemistry closely correlated with the levels of urinary KIM-1 (r = 0.553, P = 0.032). Renal survival was significantly worse in patients with elevated urinary KIM-1 (P = 0.020). CONCLUSION: Urinary KIM-1 may be a useful biomarker to evaluate kidney injury in IgAN.

Urinary NGAL as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Cirrhosis: A Prospective Study.

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 µg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] µg/g creatinine) from prerenal AKI (45 [0, 154] µg/g) or HRS (110 [50, 393] µg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] µg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Urinary sediment cast scoring index for acute kidney injury: a pilot study.

BACKGROUND/AIMS: Urine microscopy is a useful diagnostic tool; however, the manner in which nephrologists prepare and examine urinary sediment is variable. We developed an acute kidney injury (AKI) cast scoring index (CSI) in order to standardize urinary microscopy. Further, we sought to assess the precision of this scoring system. METHODS: Urine from 30 patients with AKI consistent with the syndrome of acute tubular necrosis were collected. Sample preparation was uniform and standardized. A panel of 3 nephrologists blinded to the sample preparation were instructed to grade each slide using the AKI CSI. Subsequently, the AKI CSI was then tested in another 18 patients with AKI to determine if this score could predict nonrenal recovery. RESULTS: The inter-observer agreement index was 99.80%, with a coefficient of variation of 1.24%. Of the 90 paired observations, 98.8% fell within 2 standard deviations of the mean, signifying good agreement. The receiver operator characteristic area under the curve for AKI CSI to predict nonrenal recovery was 0.79. CONCLUSIONS: AKI CSI is a simple, novel, reliable scoring system to grade the degree of epithelial cell and granular casts present on urine microscopy. A standardized AKI CSI has the potential to incorporate urinary cast analysis into the advancing field of AKI diagnostics. These preliminary data endorse the notion that the AKI CSI may be useful in predicting renal outcomes.

[Diagnosis and follow-up of chronic kidney graft dysfunction: from DFG to new biomarkers]. / Diagnostic et suivi de la dysfonction chronique du greffon rénal: du DFG aux nouveaux biomarqueurs.

Chronic allograft dysfunction is an alteration of the renal graft's structure that causes renal function to deteriorate. It can be diagnosed histologically by the presence of interstitial fibrosis lesions and tubular atrophy beginning 3 months after transplantation. The predictive value of these lesions on graft loss is limited however. Kidney function is evaluated by measuring the glomerular filtration rate using reference methods such as urinary clearance of inulin. However, estimation of the glomerular filtration rate from plasma creatinine using the Cockroft or MDRD formulas is not a reliable marker of renal function loss in the transplantation patient; nor is it a good predictive marker of graft loss. To overcome the diagnostic and prognostic shortcomings of these traditional markers in transplantation patients, new biomarkers have been developed. Yet the advantages of these biomarkers in predicting the evolving complications of chronic allograft dysfunction as well as graft loss on the individual level now require validation.

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction.

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

[Characterization of proteinuria in patients with ulcerative colitis and therapy with aminosalicylates]. / Charakterisierung der Proteinurie bei Patienten mit Colitis ulcerosa unter der Behandlung mit Aminosalicylaten.

BACKGROUND AND PURPOSE: Patients with ulcerative colitis have a higher rate of tubular nephropathies. Data concerning the cause of these lesions is rare and inconsistent, the occurrence may be part of the disease itself or a side effect of 5-aminosalicylates (5-ASA). This study investigated proteinuria and eosinophiluria in patients with moderate ulcerative colitis under treatment with 5-ASA. PATIENTS AND METHODS: Urine specimens (microelectrophoresis and eosinophiluria) of 34 patients with acute onset of moderate ulcerative colitis who were treated only with 5-ASA as active drug were analyzed. RESULTS: Data of 27 patients could be evaluated. Twelve patients had tubular proteinuria previous to treatment. By the end of the study, urine specimens normalized in six, in further six the proteinuria remained unaltered, two patients developed proteinuria under treatment. In 14 patients, proteinuria was not detectable at any time. Eosinophiluria was found in none of the specimens. CONCLUSION: Under treatment with 5-ASA no toxic or allergic nephropathy developed. One initially pathologic urine specimen normalized under treatment coming along with remission of the intestinal symptoms and histological findings. This indicates an association between the activity of the ulcerative colitis and might be caused by renal excretion of pro-inflammatory cytokines.

Clinical acute renal failure: diagnosis and management.

Acute renal failure (ARF) is frequently encountered in the hospitalized setting. In this article, we discuss the etiology, pathogenesis, preventative therapies, and renal replacement strategies in patients with acute tubular necrosis, the most common form of hospitalized ARF.

Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase.

Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potential risk for the kidneys by predisposing to acute kidney injury (AKI), specifically by lowering the toxicity threshold for a second nephrotoxin. With this purpose rats were treated with a single sub-nephrotoxic dosage of cisplatin (3mg/kg, i.p.) and after two days, with a sub-nephrotoxic regime of gentamicin (50mg/kg/day, during 6 days, i.p.). Control groups received only one of the drugs or the vehicle. Renal function and renal histology were monitored throughout the experiment. Cisplatin treatment did not cause any relevant functional or histological alterations in the kidneys. Rats treated with cisplatin and gentamicin, but not those under single treatments, developed an overt renal failure characterized by both renal dysfunction and massive tubular necrosis. In addition, the urinary excretion of fumarylacetoacetase was increased in cisplatin-treated animals at subtoxic doses, which might be exploited as a cisplatin-induced predisposition marker. In fact, the urinary level of fumarylacetoacetase prior to the second nephrotoxin correlated with the level of AKI triggered by gentamicin in predisposed animals.

Urinary interleukin-18 is a marker of human acute tubular necrosis.

BACKGROUND: Interleukin-18 (IL-18) is a mediator of ischemic acute tubular necrosis (ATN) in mice. METHODS: IL-18 was measured in human urine to determine whether it might serve as a marker of ATN. Seventy-two patients, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases, were studied. RESULTS: Patients with ATN had significantly greater median urinary IL-18 concentrations than those with all other conditions: patients with ATN, 644 pg/mg creatinine (mean, 814 +/- 151 [SE] pg/mg creatinine; P <0.0001) versus healthy controls, 16 pg/mg creatinine (mean, 23 +/- 9 pg/mg creatinine); patients with prerenal azotemia, 63 pg/mg creatinine (mean, 155 +/- 68 pg/mg creatinine); patients with urinary tract infection, 63 pg/mg creatinine (mean, 149 +/- 110 pg/mg creatinine); those with chronic renal insufficiency, 12 pg/mg creatinine (mean, 84 +/- 45 pg/mg creatinine); and patients with nephrotic syndrome, 34 pg/mg creatinine (mean, 67 +/- 47 pg/mg creatinine). Median urinary IL-18 concentrations measured in the first 24 hours after kidney transplantation were 924 pg/mg creatinine (mean, 1,199 +/- 187 pg/mg creatinine) in patients who received a cadaveric kidney that developed delayed graft function compared with 171 pg/mg creatinine (mean, 367 +/- 102 pg/mg creatinine) in patients who received a cadaveric kidney with prompt graft function and 73 pg/mg creatinine (mean, 176 +/- 107 pg/mg creatinine) in patients who received a kidney with prompt graft function from a living donor (P <0.002). In kidney transplant recipients, lower urinary IL-18 levels were associated with a steeper decline in serum creatinine concentrations postoperative days 0 to 4 (P = 0.009). CONCLUSION: IL-18 levels are elevated in urine in patients with ATN and delayed graft function compared with other renal diseases. Urinary IL-18 may serve as a marker for proximal tubular injury in ATN. The clinical application of this test may be substantial because it is reliable, inexpensive, and easy to perform.

Urinary measurement of Na+/H+ exchanger isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF.

BACKGROUND: It has been shown that apical sodium transporters of the renal tubule can be detected by immunoblotting of urine membrane fraction from rats. We raised the hypothesis that protein levels of the Na+/H+ exchanger isoform 3 (NHE3), the most abundant apical sodium transporter in renal tubule, should be increased in urine of patients presenting with acute renal failure (ARF) with severe tubular cell damage and thus might be a noninvasive marker of acute tubular necrosis (ATN). METHODS: Sixty-eight patients admitted to the intensive care unit were studied prospectively (54 patients with ARF, 14 controls without renal dysfunction). Patients with ARF were divided into 3 subgroups as follows: prerenal azotemia, ATN, and intrinsic ARF other than ATN. Urinary NHE3 protein abundance was estimated from semiquantitative immunoblots of urine membrane fraction samples collected from patients. The amount of urinary NHE3 was compared with the fractional excretion of sodium (FeNa) and urinary retinol-binding protein (RBP). RESULTS: NHE3 was not detected in urine from controls. Levels of urinary NHE3 normalized to urinary creatinine level were increased in patients with prerenal azotemia and 6 times as much in patients with ATN, without overlap (ATN, 0.78 +/- 0.36; prerenal azotemia, 0.12 +/- 0.08; P < 0.001). Conversely, urinary NHE3 protein was not detected in patients with intrinsic ARF other than ATN. Normalized NHE3 level correlated positively with serum creatinine level in patients with tubular injury (R2 = 0.305; P = 0.0003). Values for FeNa and normalized urinary RBP did not discriminate ATN from intrinsic ARF other than ATN and prerenal azotemia, respectively. CONCLUSION: In patients with ARF, urinary NHE3 abundance might be a novel noninvasive marker of renal tubule damage, helping to differentiate prerenal azotemia, ATN, and intrinsic ARF other than ATN.

Spectrum of renal tubular damage in renal failure secondary to cirrhosis and fulminant hepatic failure.

Measurements of urinary lysozyme were used to evaluate renal tubular integrity in 34 patients with cirrhosis or fulminant hepatic failure who had developed renal impairment. In 18 of the patients the lysozyme values were normal but in the remaining 16 were increased, supporting previous concepts that renal failure complicating hepatocellular disease may occur both without and with tubular necrosis. The lysozyme values were inversely related to the creatinine clearance, suggesting that the development of tubular necrosis may be determined by the level of renal perfusion. The validity of simpler laboratory tests often used to assess renal tubular integrity--namely, the urine sodium concentration, the urine:plasma osmolality ratio, and casts in the urine sediment--was evaluated by comparison with the lysozyme measurements. The urine sodium concentration was of most value and the findings in the sediment were of no value at all.

The influence of the contralateral kidney upon recovery from unilateral warm renal ischemia.

Unilateral warm renal ischemia of 90 min duration was induced in rats and the contralateral normal kidney was removed either immediately or after 1, 2, 4 or 14 d. Contralateral nephrectomy at 2, 4, 14 d increased survival and modified the functional and morphological events of the recovery period. Optimal recovery was obtained by 4 d delay. When contralateral nephrectomy was delayed by 14 d, scarring of the ischemic kidney was more severe suggesting that regeneration of damaged nephrons was impaired when renal homeostasis was sustained by the contralateral kidney. Such biphasic and inverse effects of normal kidney tissue are likely to be important determinants of the natural history of severe unilateral renal damage.

Analysis of urinary sediment by transmission electron microscopy. An innovative approach to diagnosis and prognosis in renal disease.

Urinary sediment TEM is capable of unequivocally demonstrating renal tubule cells and distinguishing them from urinary tract epithelial cells. The renal tubule cells and the accompaniments including myeloid bodies, inflammatory cells, or fibrin permit, in a particular clinical setting, synthesis of a meaningful renal diagnosis. Sequential TEM sediment studies can clarify ambiguities in diagnosis. Precisely, when much difficulty is experienced in distinguishing ATN from aminoglycoside nephrotoxicity in a patient with sepsis who has received aminoglycoside, urinary sediment TEM can facilitate the differential diagnosis with confidence. In another clinical setting, such as hypersensitivity acute interstitial nephritis, TEM urinary sediment has an irrevocable place by exhibiting the characteristic eosinophil granules that will confirm the above diagnosis, or deny it when they are absent. The morphologic features in the renal tubule cells in the sediment reflect similar changes in the tubular cells in renal tissue. Therefore, the severity of tubular changes are commensurate with the clinical outcome in terms of renal function recovery, need of dialysis, and mortality. The degree of correlation is significant. Thus, slight or no TEM sediment tubular changes signifies a good prospect for renal function recovery and low or no mortality. Conversely, severe tubular changes in the TEM sediment denote persistent renal failure accompanied by high mortality. Furthermore, the most severe tubular changes, found in hepatorenal syndrome, are consistent with its dismal prognosis.