Repeated administration of low-dose cisplatin in mice induces fibrosis.

Cisplatin, a chemotherapeutic used for the treatment of solid cancers, has nephrotoxic side effects leading to acute kidney injury (AKI). Cisplatin cannot be given to patients that have comorbidities that predispose them to an increased risk for AKI. Even without these comorbidities, 30% of patients administered cisplatin will develop kidney injury, requiring the oncologist to withhold or reduce the next dose, leading to a less effective therapeutic regimen. Although recovery can occur after one episode of cisplatin-induced AKI, longitudinal studies have indicated that multiple episodes of AKI lead to the development of chronic kidney disease, an irreversible disease with no current treatment. The standard mouse model of cisplatin-induced AKI consists of one high dose of cisplatin (>20 mg/kg) that is lethal to the animal 3 days later. This model does not accurately reflect the dosing regimen patients receive nor does it allow for the long-term study of kidney function and biology. We have developed a repeated dosing model whereby cisplatin is given once a week for 4 wk. Comparison of the repeated dosing model with the standard dosing model demonstrated that inflammatory cytokines and chemokines were induced in the repeated dosing model, but levels of cell death were lower in the repeated dosing model. The repeated dosing model had increased levels of fibrotic markers (fibronectin, transforming growth factor-ß, and α-smooth muscle actin) and interstitial fibrosis. These data indicate that the repeated dosing model can be used to study the AKI to chronic kidney disease progression as well as the mechanisms of this progression.

[Management of a patient in condition of preterminal chronic renal insufficiency as criterion for probability assessment of risk factors].

It was modified the instant method of Caplan-Meiyer (worked out for the characteristic of the patients revealing) for calculation of a new criterion--preservation of the patient in the condition pre terminal chronic renal insufficiency (CRI). It was determined 102,5; 112,5; 122,5; 132,5; 142,5; 152,5; 162,5; 172,5; 182,5; 192,5; 202,5; 212,5; 222,5; 232.5; 242,5-monthly preservation of the patient in the condition pre terminal CRI, which was formed: (98.0 +/- 1.1)%, (92.8 +/- 1.8)%, (85.6 +/- 2.1)%, (75.9 +/- 2.4)%, (62.8 +/- 2.7)%, (51.0 +/- 2.5)%, (39.9 +/- 2.4)%, (30.7 +/- 2.1)%, (22.9 +/- 1.9)%, (17.0 +/- 1.6)%, (11.8 +/- 1.5)%, (7.9 +/- 1.3)%, (4.6 +/- 1.1)%, (1.9 +/- 0.6)%. It was shown that size of this parameter changed considerably subject to the initial reason of CRI the patient sex, adequateness of the medical providing, from harmful habits (smoking) and the presence of accompanying pathologies (comorbidity coefficient).

Evolutive study of children with diffuse mesangial sclerosis.

Diffuse mesangial sclerosis (DMS) is a renal disease that usually presents as a nephrotic syndrome. It is characterized by early onset and rapid progression to end-stage renal disease, and can occur as an isolated finding or as part of the Denys-Drash syndrome. The aim of this study was to characterize clinical features and outcomes of DMS in a cohort of children. We retrospectively analyzed all cases of DMS diagnosed in our hospital between 1973 and 2008 and evaluated the progression of the disease in relation to different variables. We studied 14 patients, four with incomplete Denys-Drash syndrome and one with Frasier syndrome. All patients developed renal failure. Eight patients received a renal transplant with no relapse of the disease. Bilateral nephrectomy was performed in nine patients with end-stage renal disease. Seven patients died, with sepsis being the main cause of death. Diffuse mesangial sclerosis must be suspected in a child that presents with early onset proteinuria and/or rapidly progressive renal failure. Karyotype and WT1 gene analysis should be performed because of the predisposition of patients to develop different types of tumors. This nephropathy has a poor prognosis, but the survival rate has improved in the last decade.

Association of serum adiponectin levels with all-cause mortality in hemodialysis patients.

OBJECTIVE: Adiponectin (ADPN) has been shown to protect against cardiovascular disease for the general population with problematic metabolic syndrome. However, it remains unclear whether ADPN is associated with mortality in patients on maintenance hemodialysis (HD). METHODS, PATIENTS OR MATERIALS: We selected 85 HD patients [51 men/34 women; mean age, 64+/-2 years; underlying kidney diseases, diabetic nephropathy in 36 patients (42.3%), chronic glomerulonephritis in 29 (34.1%), hypertensive nephrosclerosis in 10 (11.8%), and others in 10 (11.8%)] who survived for more than 3 months after the start of HD. We first measured serum ADPN levels and prospectively followed patients for the next 3 years. RESULTS: We were able to follow 74 of 85 patients; 59 survived, and 15 died. Serum log-transformed ADPN levels were negatively correlated with BMI (r=-0.43, p<0.01). Despite a similar BMI (20.7+/-0.8 vs. 20.3+/-0.4 kg/m(2)), the expired patients had significantly higher ADPN compared with the surviving patients (20.5 microg/ml [14.0-23.5] vs. 14.2 microg/ml [9.7-21.3], p<0.05). Cox-hazards multivariate regression analysis adjusted for conventional case-mix features (age, sex, and underlying kidney disease) revealed that serum ADPN became a significant determinant of all-cause mortality. There was a 10.3% risk increment for each 1-microg/ml increase in ADPN during the follow-up. Kaplan-Meier analysis revealed that patients with higher ADPN levels (> or =15 microg/ml) had a significantly lower survival rate compared with those with lower ADPN levels (<15 microg/ml) (76 vs. 92%, p<0.05). CONCLUSION: These results indicated that high rather than low ADPN independently predict total mortality in HD patients.

Cytomegalovirus infection in renal transplant recipients is associated with impaired survival irrespective of expected mortality risk.

Cytomegalovirus (CMV) infection and CMV disease are associated with increased mortality post-transplantation. We have thus retrospectively examined whether this association is found both in patients with high and low mortality risk. Between 1994 and 1997, 471 kidney transplant recipients were monitored once weekly for CMV pp65 antigenemia and CMV disease the first 100 d after tx and followed prospectively for median 66.6 months. Patients with nephrosclerosis, diabetic nephropathy and amyloidosis were selected as high mortality risk groups (HRG). Overall and cardiovascular mortality beyond 100 d in the low-risk group (n = 372) was 14% and 3.5%, and in the HRG (n = 99) 31% and 16%, respectively. The effects of CMV infection and disease, recipient age and gender, panel-reactive cytotoxic antibodies, acute rejection, HRG, and graft loss in the whole study period were tested on overall mortality beyond 100 d in multiple analysis. HRG was independently associated with overall mortality, RR = 2.03, and still both CMV infection and disease were significant risk factors for mortality, independent of HRG. The same analysis was repeated for HRG (n = 99). Even in this small group CMV disease was independently associated with overall mortality. These data indicate that CMV increase mortality independently both in patients with otherwise high- or low-risk for long-term mortality.

Benign nephrosclerosis: incidence, morphology and prognosis.

AIMS: Study of benign nephrosclerosis (BNS) is often mixed up with IgA nephritis (IgAN) associated with hypertension or thin basement membrane disease (TBMD). Here we examined the clinicopathological features, incidences and prognosis of decompensated BNS. MATERIALS AND METHODS: BNS was identified in 590 (8.3%) adult cases among 7,108 renal biopsies of a mean age of 56.5 years (male: female ratio = 2.5:1). The post-biopsy follow-up period ranged from 3 to 22 years (10.1 +/- 4.6 years). RESULTS: Patients with progressive BNS were more likely to develop end-stage renal disease within 5 years of biopsy. Poor prognostic factors included poor or no control of arterial blood pressure by anti-hypertensive drugs, global glomerulosclerosis (GS) (> or = 41%) at biopsy, presence of collapsed glomeruli and/or segmented or semi-global GS. Tubulointerstitial damage, glomerular hypertrophy and loop dilatation were secondary to GS. Gender, duration of HT and onset of HT to biopsy were not significant factors. CONCLUSION: GS in BNS is due to ischemia induced by luminal narrowing or obstruction of preglomerular vessels, and glomerular HT due to loss of autoregulation in preglomerular vessels (irregularly shaped atrophic or segmented medial smooth muscle cells, with expansion of extracellular matrix with or without fibrous intimal thickening). GS resulted in luminal dilatation. Both pathological changes affecting the glomerulus may occur in the same kidney and different nephron units.

The kidney as part of the cardiovascular system.

Renal vascular damage caused by arterial hypertension brings about changes in the systemic vascular function and structure. Nephrosclerosis appears to run in parallel with systemic atherosclerosis, accounting for the increased cardiovascular morbidity and mortality in hypertensive patients. Parameters indicating a change in renal function (increased serum creatinine concentration, proteinuria, and microalbuminuria) are independent predictors of increased cardiovascular morbidity and mortality and must therefore be considered in the classification of cardiovascular risk in hypertensive patients.

Cardiovascular causes of death at Tshepong Hospital in 1 year, 1989-1990. A necropsy study.

Cardiovascular disease is the third most common cause of death in Tshepong Hospital in the western Transvaal, and the most common cause of death in patients older than 35 years. A prospective study was undertaken which included limited necropsies in 90 of the 167 cardiovascular disease deaths over 1 year. A reliable mortality pattern for cardiovascular deaths is described. Additionally, attention is paid to co-existing conditions. Conditions relating to cardiovascular disease, such as hypertension, benign hypertensive nephrosclerosis, atherosclerosis and obesity, were also evaluated. Cerebrovascular conditions were found in 32% of cardiovascular deaths. Intracerebral haemorrhage was found in 50% and cerebral infarction in 29% of cases. Fifty-seven per cent of cardiovascular deaths were due to cardiac conditions, the most common being pulmonary hypertension (31%), dilated cardiomyopathy and chronic rheumatic valvular disease (17% each) and hypertensive heart disease (14%). Forty-nine per cent of subjects were hypertensive, while 40% exhibited benign nephrosclerosis and only 3% of the examined vessels had signs of severe atherosclerosis. Tuberculosis was present in 13% of cases. The clinical diagnosis was the same as the final necropsy diagnosis in 38% of cases. These results emphasise the importance of performing necropsies to obtain reliable mortality statistics.

Late somatic effects in mice after total lymphoid irradiation.

Late somatic effects of total lymphoid irradiation have been investigated in BC3F1 mice. A total X-ray dose of 34 Gy was distributed in 17 daily fractions. The cumulative mortality curve is shifted in time because all the irradiated mice died earlier than the unirradiated controls. There was a 24% shortening of life span. A marked increase of solid tumor incidence, mostly due to skin cancers, was observed (66% vs 30%). In contrast, the incidence of malignant lymphomas was greatly reduced in irradiated mice (6% vs 49%). Furthermore, nephrosclerosis was a common finding in the irradiated group (38% vs 8%). Death-rate analysis revealed an association between life shortening and the presence of solid tumors and nephrosclerosis at death.

Mortalidad por nefroangiosclerosis arterial maligna en Ciudad de la Habana: informe preliminar / Mortality due to malignant arterial nephroangiosclerosis in Havana City: preliminary report

Se estudia la mortalidad por nefroangiosclerosis arterial maligna (NAM) diagnosticada por autopsia en 10 de los principales hospitales clinicoquirúrgicos de adultos de Ciudad de La Habana, en el trienio de 1980 a 1982.En 16 738 protocolos de autopsias encuestados se encontró el diagnóstico de NAM en 193 casos, para el 1.15

Mortalidad por nefroangiosclerosis arterial maligna en Ciudad de la Habana: informe preliminar / Mortality due to alignant arterial nephroangiosclerosis in Havana City: preliminary report

Se estudia la mortalidad por nefroangiosclerosis arterial maligna (NAM) diagnosticada por autopsia en 10 de los principales hospitales clinicoquirúrgicos de adultos de Ciudad de La Habana, en el trienio de 1980 a 1982.En 16 738 protocolos de autopsias encuestados se encontró el diagnóstico de NAM en 193 casos, para el 1.15

Blood pressure, nephrosclerosis, and age autopsy findings from the Honolulu Heart Program.

The aspect of nephrosclerosis reflected by fibrous intimal thickening of small arteries (arteriosclerosis) was measured by a newly introduced morphometric procedure in 154 autopsies of Japanese-American men in Honolulu. These men were subjects of the Honolulu Heart Program and had previously been assessed for blood pressure and other clinical characteristics in a prospective study. In periodic acid-Schiff (PAS)-stained sections of renal cortex, measurements were made of interlobular artery diameters and intimal thicknesses. Vessels of outer diameter 80 to 130 microns and 160 to 300 microns were examined separately and are called the "remote" and "close" levels of the interlobular arteries, respectively, defined in relation to the heart. Nephrosclerosis thus quantified, together with age, could be used to predict the levels of blood pressure (BP) to be found in retrospective review of past records. The mathematical function obtained in a former study to make these predictions was found to predict the observed levels of blood pressure to an acceptable degree in the groupings that involved 92% of the subjects. Verification of that formerly obtained predictive function is now claimed. Correlation coefficients relating BP to close and remote measures were about of equal magnitude (r = 0.34 and 0.40, respectively). Subjects with cardiovascular-renal causes of death differed in both nephrosclerosis and blood pressure from subjects whose cause of death was unrelated to cardiovascular-renal diseases; the two factors taken together each contributed significantly to the cause of death difference. Correlations between nephrosclerosis and aortic atherosclerosis were stronger than could be explained solely by a linkage to observed values of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Mortalidad por nefroangioesclerosis maligna en Cuba: informe preliminar de las primeras 7 provincias encuestadas / Mortality due to alignant nephroangioesclerosis in Cuba: preliminary report of the first seven surveyed provinces

Se revisan los protocolos de autopsias de 17 hospitales clinicoquirúrgicos docentes de adultos en 7 provincias, de los años 1980, 1981 y 1982. De un total de 33 109 protocolos revisados se encontraron 297 casos con el diagnóstico de nefroangioesclerosis maligna como acusa directa o contribuyente de muerte, para una incidencial del 0,90

(varió entre 0,21

en Cienfuegos y 1,15

en Ciudad de la Habana (AU)

Mortalidad por nefroangioesclerosis maligna en Cuba: informe preliminar de las primeras 7 provincias encuestadas / Mortality due to malignant nephroangioesclerosis in Cuba: preliminary report of the first seven surveyed provinces

Se revisan los protocolos de autopsias de 17 hospitales clinicoquirúrgicos docentes de adultos en 7 provincias, de los años 1980, 1981 y 1982. De un total de 33 109 protocolos revisados se encontraron 297 casos con el diagnóstico de nefroangioesclerosis maligna como acusa directa o contribuyente de muerte, para una incidencial del 0,90 % (varió entre 0,21 % en Cienfuegos y 1,15 % en Ciudad de la Habana

Long-term survival after recovery from malignant nephrosclerosis.

Five patients with malignant nephrosclerosis (MNSC) and severe renal failure (mean plasma creatinine 926 micromoles/L) were followed for 52 to 83 months. Blood pressure was controlled by a minoxidil-nadolol-diuretic combination. Combined renal length (CRL) on presentation was greater than 18 cm in four patients and 15.3 cm in one patient. Plasma creatinine values declined into the second year, and improved function persisted into the third and fourth years after presentation. The patient with least renal mass on presentation had evidence of declining renal function at 60 months. The data suggest that CRL and sustained blood pressure control are critical determinants of both short- and long-term recovery and preservation of self-sustaining renal function in patients with MNSC.

[The bilateral nephrectomy in terminal renal disease (author's transl)]. / Einzeitige bilaterale Nephrektomie bei terminaler Niereninsuffizienz.

45 cases of nephrectomy are reported. Mortality was 8.9%. Thirty-one had a drug-resistant, severe hypertension, three had infected kidneys, and in eleven cases nephrectomy was performed prior to transplantation. Although blood pressure improved in all patients, of the first group 24% died within one year after nephrectomy, which shows unsatisfactory prognosis of malignant nephrosclerosis. Only early nephrectomy can lead to better results. Routine nephrectomy before transplantation should be avoided. Indications for this group are discussed.

Arteriolar nephrosclerosis in the Syrian hamster.

Syrian hamsters developed spontaneous renal lesions that resembled those of arteriolar nephrosclerosis in man, and differed from other spontaneously occurring or virus-induced renal diseases in other rodent species. Morphologic changes were mainly degenerative with little cellular exudation and were associated with histologic changes in the intrarenal vasculature. The renal lesions were progressive, often fatal and sometimes were complicated by glomerular amyloidosis with the nephrotic syndrome and uremia. Endstage kidneys often had fibrinoid necrosis of intrarenal arterioles and thus resembled lesions characteristic of the malignant phase of human essential hypertension. Fibrinoid necrosis of small arterioles was common in the uterus, ovaries or testes of affected animals; it was less frequent in mesenteric or coronary vessels. Cardiac thrombosis, often involving the left atrium or left atrioventricular valves, also was common. Changes occurred earlier and often were more severe in females than in males. This disease was a major cause of morbidity and mortality and hampered life-span studies.