Plasma Neutrophil Gelatinase-Associated Lipocalin as a Marker of Tubular Damage in Diabetic Nephropathy

BACKGROUND: An increase in neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular injury. Diabetic nephropathy causes typical changes in the kidney, characterized by glomerulosclerosis and eventual tubular damage. We validated the usefulness of plasma NGAL (pNGAL) as a biomarker of tubular damage in patients with diabetic nephropathy. METHODS: We included 376 patients with diabetes mellitus (260 patients with chronic renal insufficiency who had not received hemodialysis and 116 hemodialyzed due to diabetic nephropathy) and 24 healthy controls. Patients with chronic renal insufficiency were divided into three groups according to urinary albumin excretion (UAE) levels. pNGAL levels were measured using the Triage NGAL test (Alere, San Diego, CA, USA) and were compared between groups. We also examined whether pNGAL level was related to the degree of albuminuria and cystatin C-based glomerular filtration rate (GFR). RESULTS: Mean pNGAL levels of the healthy controls, chronic renal insufficiency patients with diabetes mellitus, and hemodialyzed patients were 61.9±5.3 ng/mL, 93.4±71.8 ng/mL, and 1,536.9±554.9 ng/mL, respectively. pNGAL level increased significantly in patients with severe albuminuria (P < 0.001) and had a moderate correlation with the degree of albuminuria (r=0.467; P < 0.001) and GFR (r=0.519; P < 0.001). Multivariate regression analysis showed that the pNGAL level was associated with tubular damage independent of patient age, sex, and GFR. CONCLUSIONS: pNGAL level independently reflects the degree of tubular damage in patients with diabetic nephropathy. Measurement of pNGAL, combined with UAE, would enable simultaneous, highly reliable assessments of tubular damage for such patients.

Quantitative evaluation of renal parenchymal perfusion using contrast-enhanced ultrasonography in renal ischemia-reperfusion injury in dogs

This study evaluated whether renal perfusion changes can be noninvasively estimated by using contrast-enhanced ultrasonography (CEUS) in renal ischemia-reperfusion injury and investigated the correlation between renal perfusion measured by CEUS and necrosis and apoptosis of renal tubular epithelial cells. In six dogs with experimentally induced renal ischemia-reperfusion injury, changes in time to peak intensity, peak intensity, and area under the curve were measured on CEUS. Peak intensity and area under the curve of the renal cortex began to decrease on day 1 (about 20% lower than baseline) and reached the lowest levels (about 50% of baseline) on day 4. They then gradually increased until day 10, at which time peak intensity was about 87% and area under the curve was about 95% of baseline; neither fully recovered. Both parameters were strongly correlated with the necrosis scores on histopathologic examination on day 4 (r = −0.810 of peak intensity and r = −0.886 of area under the curve). CEUS allowed quantitative evaluation of perfusion changes in acute renal ischemia-reperfusion injury, and CEUS results were correlated with renal tubular damage on histopathologic examination. Thus, CEUS could be a noninvasive, quantitative diagnostic method for determining progress of renal ischemia-reperfusion injury.

Pharmaceutical care of five cases of hypophosphatemic osteomalacia secondary to renal tubular damage caused by adefovir / 中国药学杂志

OBJECTIVE: To summarize the outcomes and clinical features of hypophosphatemic osteomalacia secondary to renal tubular damage caused by adefovir and put forword the key points of pharmaceutical care for these patients. METHODS: Literature was retrieved about hypophosphatemic osteomalacia secondary to renal tubular damage caused by adefovir in recent years. Combining the clinical situations of five patients with the named damage, they were treated with complement of phosphorus preparations and monitored for related clinical indicators. RESULTS: The possible mechanisms of adefovir for causing hypophosphatemic osteomalacia secondary to renal tubular damage is gene defect. Hypophosphatemic osteomalacia often occurrs in patients taking small doses (10 mg · d-1) of adefovir for more than one year. The symptoms aggravate over time. By withdrawing adefovir or switching to other antiviral drugs and giving syptomatic treatment with phosphorus, calcium, and vitamin D supplements and other measures, good prognosis was achieved. CONCLUSION: Hypophosphatemic osteomalacia secondary to renal tubular damage caused by adefovir is lack of specific clinical features, which is easy to be misdiagnosed, therefore attention should be paid by clinical professionals.

Value of combined utilization of urinary CysC and NAG in the diagnosis of renal tubules damage / 国际检验医学杂志

Objective To discuss the diagnostic value of combined utilization of urinary cystatin C (CysC) and β‐N‐acetyl‐glu‐cosaminidase (NAG) in renal tubules injury .Methods Urine samples were collected from 130 cases of patients with renal tubular damage (case group) and 100 cases of health individuals (normal control group) ,respectively .The concentration of CysC and the activity of NAG in urine were detected .Results The sensitivity ,specificity ,and positive predictive value of combined utilization of CysC and NAG in diagnosis of renal tubules damage were 85 .4% ,89 .6% and 82 .1% ,respectively .The concentration of CysC and the activity of NAG in case group after treatment were both significantly different from those before treatment (P<0 .05) .Conclu‐sion Combined utilization of urinary CysC and NAG has a significant value for the diagnosis and the therapeutic monitoring in re‐nal tubules injury .

Effect of Stem Cell Therapy on Adriamycin Induced Tubulointerstitial Injury

BACKGROUND AND OBJECTIVES: It was postulated that adriamycin (ADR) induce renal tubulointerstitial injury. Clinicians are faced with a challenge in producing response in renal patients and slowing or halting the evolution towards kidney failure. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on tubular renal damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. METHODS AND RESULTS: Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy, vacuolated cytoplasm, dark nuclei, detached epithelial lining and desquamated nuclei were noticed in few collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of CT showing desquamated nuclei and mean value of serum creatinine revealed significant difference in ADR group. The mean area% of Prussian blue+ve cells and that of CD105 +ve cells measured in subgroup S1 denoted a significant increase compared to subgroups S2 and S3. CONCLUSIONS: ADR induced tubulointerstitial damage that regressed in response to cord blood HMSC therapy.

Evaluation of Plasma Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Tubular Damage in Diabetic Nephropathy / 임상검사와정도관리

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has recently been introduced as a renal biomarker and an increase in its level suggests tubular injury. Diabetic nephropathy, a leading cause of end-stage renal disease, causes typical changes characterized by glomerulosclerosis and eventual tubular damage in the kidney. In the present study, we attempted to validate the usefulness of plasma NGAL (pNGAL) as a biomarker for tubular damage in diabetic nephropathy. METHODS: The plasma NGAL levels of 260 diabetes mellitus patients and 50 healthy individuals werewas measured by means of fluorescent immunoassay using with the Triage NGAL test (Biosite, USA). The patients were divided into 3 groups on the basis of their urinary albumin excretion (UAE) levels, and the pNGAL differences among each group were analyzed. The degree of albuminuria and cystatin C-based glomerular filtration rate (GFR) were also compared with the pNGAL levels. RESULTS: The mean pNGAL levels of the normal subjects and diabetic patients were 61.9 +/- 4.81 ng/mL and 93.4 +/- 71.78 ng/mL, respectively. pNGAL level was significantly increased in patients with severe albuminuria (P < 0.001). The pNGAL level was found to be positively correlated with the degree of albuminuria (R2 = 0.218, P < 0.001) and inversely correlated with GFR (R2 = 0.269, P < 0.001). Particularly, the pNGAL level of patients with diabetic nephropathy was found to be associated with the renal damage and independent of other factors influencing the renal damage (R2 = 0.218). CONCLUSIONS: pNGAL level independently reflects renal damage in patients with diabetic nephropathy. Measurement of pNGAL level combined with UAE would help enable to detect both glomerular and tubular damage in diabetic nephropathy patients.

A trying to evaluate acute renal tubular damage after ESWL / 대한비뇨기과학회지

Determination of urinary marker proteins was carried out trying to evaluate renal tubular damage as a part of renal injury caused by ESWL via EDAP LT-01+lithotiptor. All of twenty patients undergoing ESWL, suffered from unilateral, nonobstructive, infection-free, and previously untreated renal stone (s). Two urinary marker proteins, N-acetyl-beta-gluoosaminidase (NAG) and beta 2-micmglobulin (beta2-M) were monitored in all the patients 1 day before, 1 and 3 day (s) after ESWL using total 100 storage of 3 sessions which is average therapeutical dose. Urinary level or NAG (normal value; 0.29-7.23 U/L) was 1.66+/-1.31 1 day before, 1.97+/-1.57, 2.66+/-2.90 U/L 1 and 3 day (s) after ESWL respectively. beta2-M level (normal value <300 ug/L) was 142+/-137 1 day before. 133+/-100, 151+/-186 ug/L 1 and 3 day(s) alter ESWL, respectively. Consequently it was concluded that ESWL using average therapeutical dose (100 storage) via EDAP LT-01+ litholriptor can hardly develop renal tubular damage.