Risk factors of hyperparathyroidism in advanced stages of chronic kidney disease.

The pathogenesis of renal osteodystrophy is not clearly defined. We evaluate in this study the potential effect of demographic and biochemical markers on parathormone (PTH) level in patients with chronic kidney disease (CKD) stages 4 and 5. We retrospectively studied 138 patients with CKD stages 4 and 5 selected from the database of the Sheffield Kidney Institute in the interval from 1996 to 2005. All patients had baseline as well as follow-up levels of PTH, adjusted serum calcium, phosphate, calcium phosphorus product, albumin, bicarbonate and estimated glomerular filtration rate (eGFR). At baseline, serum albumin, eGFR and adjusted serum calcium levels significantly negatively correlated with PTH serum levels. Adjusted serum calcium levels at last follow-up remained a significant negative predictor of PTH levels; however, baseline PTH levels demonstrated a significant positive correlation with final serum PTH levels. This study high lights the significance of serum PTH levels at presentation on the long-term effect of parathyroid gland function. This reinforces the need for early intervention to achieve optimal control of hyperparathyroidism in CKD patients.

Conservatively managed patients with stage 5 chronic kidney disease--outcomes from a single center experience.

BACKGROUND: Limited survival data are available on chronic kidney disease stage 5 (CKD 5) patients who opt for conservative management rather than dialysis. AIM: To measure survival in such patients and investigate potential factors predicting survival. DESIGN: Retrospective survival analysis of a cohort of conservatively managed CKD 5 patients from a single center. METHODS: Survival was measured in 69 conservatively managed patients from the time they were first known to have CKD 5. Comorbidities, residual renal function and other laboratory parameters (calcium, phosphate, parathyroid hormone, albumin and hemoglobin) and blood pressure were recorded. RESULTS: Overall median patient survival from the time of first known CKD 5 was 21 months. Patients known to a nephrologist before reaching CKD 5 survived longer (median 32 months) than those presenting with CKD 5 (15 months, P = 0.025). Serum albumin >35 g/l was associated with greater survival, but other biochemical parameters, comorbidity grade and age did not predict survival. CONCLUSION: These survival data provide useful information for nephrologists counseling CKD 5 patients considering whether to pursue dialysis or conservative management. Risk factors that correlate with survival in the dialysis population may not predict survival in conservatively managed CKD 5 patients.

The impact of topical phenytoin on recalcitrant neuropathic diabetic foot ulceration.

OBJECTIVE: To study the impact of topical phenytoin on the healing of recalcitrant neuropathic diabetic foot ulcers in patients with no clinical evidence of ischaemia or infection, and to evaluate its antibacterial effect. METHOD: Thirty-two patients were enrolled into the study. Topical phenytoin in the form of 2% aerosol powder was applied once daily in addition to the patient's usual treatment (weekly sharp debridement, offloading and use of a gauze dressing) for eight weeks. The primary outcome was change in ulcer area over time, measured by grid tracing. Secondary outcomes were the ability of topical phenytoin to eradicate bacterial isolates, and the occurrence of adverse events. RESULTS: Topical phenytoin significantly improved healing of recalcitrant neuropathic diabetic foot ulcers. Baseline wound area was 319.3 + 340.4 mm2, reducing to 286.1 + 341.1 mm2 and 269.1 + 341.2 mm2 after four and eight weeks respectively. However, the overall reduction in ulcer size was only 18.3% + 27.5% and 25.7% + 38.6 % respectively. Topical phenytoin therapy over eight weeks did not eradicate any of the bacterial wound isolates (Staphylococcus spp., Proteus spp. or Pseudomonas spp.). Of the 32 patients evaluated, only eight (25%) achieved more than 50% reduction in ulcer size after eight weeks of treatment. CONCLUSION: Topical phenytoin can enhance wound healing in recalcitrant neuropathic diabetic foot ulcers, although only one-quarter of patients achieved more than 50% reduction in ulcer size after eight weeks of therapy. Further research is needed to characterise those patients who will satisfactorily respond to such therapy.

C-K-D: more vascular damage than kidney disease.

The perceived prevalence of Chronic kidney disease (CKD) is on the increase worldwide. This has led to considerable debate and controversy as some believe such an increase reflects a genuine increase in the incidence and prevalence of CKD whilst others perceive it to be the result of the ageing of the population with the inherent decline in kidney function associated with advancing age. This review tries to reconcile both views drawing attention to the fact that the age-related decline in kidney function may not be physiological but instead a manifestation of diffuse vascular ageing and atherosclerosis affecting a number of endorgans including the kidneys. Consequently, the so-call age-related chronic kidney disease (CKD) may be better defined as Cardio-Kidney-Damage (C-K-D).

The management of CKD: a look into the future.

The increasing global prevalence of chronic kidney disease (CKD) and end-stage renal disease with the associated spiraling cost has profound public health and economic implications. This has made slowing the progression of CKD, a major health-care priority. CKD is invariably characterized by progressive kidney fibrosis and at present, treatment aiming to slow the progression of CKD is limited to aggressive blood pressure control, with few therapies targeting the fibrotic process itself. In this review, we explore the potential of experimental therapeutic strategies, based on preventing or reversing the pathophysiologic steps of kidney remodeling that lead to fibrosis.

Association of nitric oxide production and apoptosis in a model of experimental nephropathy.

BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis.

IGF-I inhibitors reduce compensatory hyperfiltration in the isolated rat kidney following unilateral nephrectomy.

BACKGROUND: A role for insulin-like growth factor-I (IGF-I) as a mediator of renal hyperfiltration and hyperperfusion following unilateral nephrectomy (UNx) has been examined. METHODS: Adult male Wistar rats were subjected to either left UNx or sham operation. Twenty one days after surgery, the right kidney was removed under barbiturate anaesthesia, and renal function was measured ex vivo using an isolated rat kidney perfusion system. The glomerular filtration rate was assessed from the renal clearance of [(14)C]inulin. RESULTS: UNx stimulated renal growth as shown by a significantly higher (P<0.02) tissue dry weight in kidneys from UNx (0.45+/-0.02 g) than from sham-operated rats (0.31+/-0.02 g). Compensatory hyperfiltration could be detected ex vivo; kidneys obtained from UNx rats having a significantly higher (P<0.05) [(14)C]inulin clearance (0.75+/-0.08 ml/min, n=8) than kidneys obtained from sham-operated animals (0.39+/-0.05 ml/min, n=8). Compensatory hyperperfusion was also detected ex vivo; kidneys obtained from UNx rats having a significantly higher (P<0.05) renal perfusate flow (28.2+/-2.7 ml/min) than kidneys obtained from sham-operated rats (22.5+/-0.8 ml/min). Following perfusion with either 50 microg monoclonal IGF-I antibody (n=4) or 6.5 microM genistein (n=4), an inhibitor of tyrosine kinase, no significant difference in [(14)C]inulin was observed between kidneys obtained from either UNx or sham-operated rats. In contrast to hyperfiltration, renal hyperperfusion remained unaffected by the IGF-I antibody and was only reduced by 30% following genistein administration. CONCLUSIONS: The results suggest a role for renal IGF-I as a mediator of compensatory hyperfiltration in the rat.

Upregulation of epidermal growth factor and its receptor in the kidneys of rats with streptozotocin-induced diabetes.

We have studied the acute changes (up to 30 days) in the expression of epidermal growth factor (EGF) and its receptor (EGFr) in the kidneys of adult male Wistar rats made diabetic by a single intravenous injection of streptozotocin (55 mg/kg) using a combination of immunocytochemical staining and in situ hybridization histochemistry. In the absence of insulin treatment, diabetic rats displayed renal growth (hypertrophy and hyperplasia). It was accompanied by an increase in immunostainable EGF within the thick ascending limb (TAL) of the loops of Henle which was apparent within 24 h of the onset of diabetes, reached a peak by day 7 and persisted to the end of the experimental period (day 30). In situ hybridization histochemistry revealed that these changes were preceded by a rapid rise in EGF mRNA in the cells of the TAL, which was highest after 1 day but declined to control levels by day 7. Increased immunostainable EGFr was evident in both the proximal and TAL and in the cortical collecting ducts from day 1. Staining of the proximal tubules declined rapidly after day 1 but that of the TAL and collecting ducts persisted until day 7 and declined thereafter. These results are discussed in light of the role of EGF in the hypertrophy and repair of the diabetic kidney.

Localization of PDGF-BB in the juxtaglomerular cells of cyclosporin-treated rats.

We have examined the ultrastructural localization of immunoreactive platelet-derived growth factor (PDGF) in Wistar rats injected with cyclosporin A (CyA, 12.5 mg/kg/day) for 4 weeks. CyA injections resulted in a significant increase in serum creatinine (47 +/- 3 vs. 35 +/- 2 mumol/l, p < 0.05) and a reduction in creatinine clearance (0.29 +/- 0.07 vs. 0.53 +/- 0.04 ml/min/100 g b.w., p < 0.01). CyA-treated rats displayed marked hypertrophy and hypergranularity of the juxtaglomerular cells. Morphometric studies showed a significant increase in the number (2.8 +/- 0.3 vs. 1.8 +/- 0.3, p < 0.05) and a 60% increase in the volume of secretion granules within these cells. PDGF was detected exclusively within the secretion granules of the juxtaglomerular cells of the afferent arterioles of CyA-treated animals. We conclude that CyA therapy or its induced haemodynamic alterations result in increased accumulation of PDGF-BB within the secretion granules of the juxtaglomerular cells.

Iodometric microgram determination of chromium(III) and (VI) by use of chemical amplification reactions.

A simple, rapid and sensitive method is described for the iodometric determination of microgram amounts of chromium(III), based on the oxidation of chromium(III) with periodate at pH 3.2, removal of the unreacted periodate by masking with molybdate and subsequent iodometric determination of the liberated iodate. Chromium(VI) can be determined by this method after prior reduction to chromium(III) with sodium sulphite. The method can also be used for the analysis of organochromium compounds.

Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease.

It is hypothesised that chronic progressive kidney disease may be mediated by abnormalities of lipid metabolism. A series of self-perpetuating secondary events follows an initial glomerular injury. Increased glomerular basement membrane permeability leads to loss of lipoprotein lipase activators, resulting in hyperlipidaemia. Circulating low-density lipoprotein binds with glycosaminoglycans in the glomerular basement membrane and increases its permeability. Filtered lipoprotein accumulates in mesangial cells and stimulates them to proliferate and produce excess basement membrane material. The proximal tubular cells metabolise some of the filtered lipoprotein and the remainder are altered on passage down the nephron. Luminal apoprotein precipitates, initiating or aggravating tubulo-interstitial disease, if the intraluminal pH is close to the isoelectric point of the apoprotein. The hypothesis offers new approaches to the study of chronic progressive kidney disease by proposing a major pathogenetic role for lipid abnormalities.

[Acute renal failure induced by sulfinpyrazone (author's transl)]. / Insuffisance rénale aiguë induite par la sulfinpyrazone.

We report on 4 cases of reversible acute renal failure (ARF), appearing within the first days after institution of a sulfinpyrazone treatment (600 mg p. day) early after a myocardial infarction. Urinary data were consistent with an acute tubular necrosis. A renal biopsy, performed in 3 patients, revealed only very discrete tubular and interstitial lesions, not helpful in the understanding of the ARF. Three pathogenetic mechanisms could be evoked. Data in favour of an acute tubular precipitation of uric acid or an immunologically induced acute interstitial nephritis are lacking. More probably this ARF is due to an inhibitory effect of sulfinpyrazone on the renal prostaglandin synthesis. Early after a myocardial infarction, renal prostaglandins could play an important protective role in maintaining the renal circulation. Renal function should be monitored closely when sulfinpyrazone is prescribed, especially early after a myocardial infarction.