Development Of Acute Tubular Necrosis Research Articles

P0594USEFULNESS OF THE NEUTROPHIL-TO-LYMPHOCYTE AND PLATELET-TO-LYMPHOCYTE RATIOS IN THE COMMUNITY-ADQUIRED ACUTE KIDNEY INJURY

Abstract Introduction and Aims The neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios have been identified as markers of inflammation and endothelial dysfunction in recent literature. Both are easily measured, reproducible and inexpensive, therefore cost-effective. To date, its usefulness as prognostic markers in community-acquired acute kidney injury (CA-AKI) has not been evaluated. The aim of this study was to analyze the usefulness of the NLR and PLR in terms of morbidity and mortality in community-acquired acute kidney injury. Method We established a cohort of 308 patients with community-acquired acute kidney injury (CA-AKI) admitted to the Nephrology service of a third level hospital from January 2010 to February 2015. NLR and PLR ratios were obtained with the levels of the first analysis performed at admission. Results We studied 308 patients with CA-AKI, 180 were men (58,4 %), mean age was 73.22 (±13,95). The mean length of stay was 12,25 days (±11,69). The etiology of CA-AKI was divided in prerenal 214 cases (69.5%); renal 71 cases (23.1%); obstructive 23 cases (7,5%). AKI KDIGO stages were stage I, 45 cases (14.6%); stage II, 34 cases (11%); stage III 229 cases (74.4%). Previous chronic kidney disease (CKD) was detected in 212 cases (68.8%). A total of 54 patients (17,15%) required hemodialysis and 38 patients died during admission (12.3%). Mean NLR was 9.14 ± 8,47 (95% IC 8,2-10,1). Mean PLR was 236,99 ± 228,41 (95% IC 211,38-262,6). NLR according to etiology was: prerenal 8,55±6,8; renal 9,37±9,8; obstructive 13,99±14,82 (significant differences of the latter group compared to the prerenal group). PLR according to etiology: prerenal 228,31±216,34; renal 236,15±233,77; obstructive 320,37±304,89 (non-significant differences). Within the group of prerenal origin, 79 cases were complicated by the development of acute tubular necrosis (ATN). These cases presented a higher NLR (NLR of ATN 10,7±10,28 vs NLR of pure prerenal 7,8±5,6; p=0,026). There were no significant differences between the PLR of the pure prerenal group and the group with ATN (225,95±262,54 vs 285,78±278,61). The NLR showed a significant correlation with the peak creatinine (r= 0,186; p = 0,001) and with the serum albumin (r= -0,237; p < 0,001). The PLR also showed correlation with the peak creatinine (r= 0,134, p = 0,018) and the serum albumin (r = 0,165, p= 0,07).The NLR, but not the PLR, was associated with the length of hospital stay (multiple linear regression analysis). Through a multivariate binary logistic regression analysis, the variables that were independently associated with mortality during admission were the Liaño individual severity index and the NLR (OR 1,060; IC 95 % 1.014 – 1,108). The variables that were ruled out by the model were sex, age, Charlson comorbidity index, peak creatinine, serum albumin, chronic kidney disease, etiology of AKI (prerenal vs. non prenal), potassium, KDIGO stage of AKI, need of hemodialysis and PLR. The best cut-off point of the NLR to predict mortality was 6,68 (AUC 0,584; sensitivity 0.60; specificity 0.58; Youden index 0.178) Conclusion In our cohort of patients affected by CA-AKI, the NLR was associated with the morbidity and the mortality during admission. More studies are need to confirm this finding, but the easiness of obtaining it and its economic cost make it cost-effective, giving the NLR a leading role in assessing the risk of CA-AKI.

Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta-analysis

Acute kidney injury (AKI) is a common complication in patients with cirrhosis that increases mortality. The most common causes of AKI in these patients are prerenal azotemia, acute tubular necrosis (ATN), and hepatorenal syndrome; it is important to determine the etiology of AKI to select the proper treatment and predict patient outcome. Urine biomarkers could be used to differentiate between patients with ATN and functional causes of AKI. We performed a systematic review and meta-analysis of published studies to determine whether urine levels of interleukin (IL)18 and lipocalin 2 or neutrophil gelatinase-associated lipocalin (NGAL) are associated with the development of ATN in patients with cirrhosis. We searched MEDLINE, Scopus, ISI Web of Knowledge, and conference abstracts through December 31, 2015, for studies that assessed urine biomarkers for detection of acute kidney injury in patients with cirrhosis or reported an association between urine biomarkers and all-cause mortality in these patients. We included only biomarkers assessed in 3 or more independent studies, searching for terms that included urine biomarkers, cirrhosis, NGAL, and IL18. We calculated the pooled sensitivities and specificities for detection and calculated the area under the receiver operating characteristic curve (AUC) values using a bivariate logistic mixed-effects model. We used the χ2 test to assess heterogeneity among studies. We analyzed data from 8 prospective studies, comprising 1129 patients with cirrhosis. We found urine levels of the markers discriminated between patients with ATN and other types of kidney impairments, with AUC values of 0.88 for IL18 (95% confidence interval [CI], 0.79-0.97) and 0.89 for NGAL (95% CI, 0.84-0.94). Urine levels of IL18 identified patients who would die in the hospital or within 90 days (short-term mortality) with an AUC value of 0.76 (95% CI, 0.68-0.85); NGAL identified these patients with the same AUC (0.76; 95% CI, 0.71-0.82). In a systematic review and meta-analysis, we found that urine levels of IL18 and NGAL from patients with cirrhosis discriminate between those with ATN and other types of kidney impairments, with AUC values of 0.88 and 0.89, respectively. Urine levels of IL18 and NGAL identified patients with short-term mortality with an AUC value of 0.76. These biomarkers might be used to determine prognosis and select treatments for patients with cirrhosis.

Acute Tubular Necrosis as a Complication of Collagenous Colitis

Introduction: Microscopic colitis is a subdiagnosed cause of chronic diarrhea, especially among the elderly, although it can occur in patients of any age. This case evidences the potential seriousness of the pathology, in particular, the development of acute tubular necrosis which could be prevented by an early diagnosis. Case Report: An 80-year-old man, previously healthy, with a history of watery diarrhea, anorexia occasional abdominal cramps and weight loss (9 kg), in the last 5 months. He was submitted to a colonoscopy 1 month before, which did not showed endoscopic lesions, and treated with loperamide, but without improvement. There was no history of joint pains or swelling, fever or use of non-steroidal antiinflammatory drugs. He recurred to the emergency department due to worsening diarrhea, asthenia and dizziness. On the physical exam he was pale and dehydrated. Laboratory tests showed iron deficiency anemia, acute tubular necrosis (creatinine of 12.8mg/dL, eGFR of 4ml/min (1.73m2) and hypokalemia (K+ 2.4mEq/L). Urinary tract infection and obstruction were excluded and he was admitted on an intensive care unit. Stool cultures were negative, including specific tests forbacteria or parasites. The presence of celiac disease was excluded with normal duodenal biopsies and negative serologic testing. An ileocolonoscopy was performed, revealing a mucosa with normal appearance. Biopsies of the right and left colon were taken and the histopathological exam was consistent with the diagnosis of collagenous colitis. He presented progressive improvement of the renal impairment, with fluids and correction of the hydroelectrolytic disorders, without the need of haemodialysis. The patient was treated with oral budesonide with resolution of diarrhea. Budesonide was stopped after 1 year of treatment. Eighteen months after the diagnosis, he is currently being followed in outpatient clinic, asymptomatic, but complaining of occasional constipation.

Acute Kidney Injury

Acute Kidney Injury

Acute Kidney Injury

1. David T. Selewski, MD* 2. Jordan M. Symons, MD† 1. *Department of Pediatrics and Communicable Diseases, Division of Nephrology, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI. 2. †Department of Pediatrics, Division of Nephrology, University of Washington School of Medicine, Seattle, WA. * Abbreviations: ACE: : angiotensin-converting enzyme AKI: : acute kidney injury AKIN: : Acute Kidney Injury Network ANCA: : antineutrophil cytoplasmic antibody ATN: : acute tubular necrosis ECG: : electrocardiogram FEurea: : fractional excretion of urea FENa: : fractional excretion of sodium KDIGO: : Kidney Disease: Improving Global Outcomes NSAID: : nonsteroidal anti-inflammatory drug RIFLE: : Risk, Injury, Failure, Loss, and End-stage The term acute kidney injury has replaced acute renal failure and represents a spectrum of clinically meaningful kidney damage. After completing this article, readers should be able to: 1. Recognize and define the spectrum of acute kidney injury (AKI). 2. Understand the diagnostic approach and be able to differentiate the main causes of AKI. 3. Understand the complications of AKI and the treatment of a child with AKI. Acute kidney injury (AKI), formerly called acute renal failure, is characterized by multiple abnormalities, including increases in serum creatinine and blood urea nitrogen, electrolyte abnormalities, acidosis, and difficulties with fluid management. We have come to realize that what was previously thought to be relatively minor damage to the kidney can have significant short-term effects on morbidity and mortality and potential long-term implications for the development of chronic kidney disease. Thus, the term acute kidney injury has replaced acute renal failure , suggesting the spectrum of kidney damage that can occur. ### Definition AKI is classically defined as an acute decrease in glomerular filtration rate, which results in an increase in serum creatinine. It is important to recognize the limitations of creatinine as a marker of AKI because an increase in creatinine can be delayed by as much as 48 hours after damage to the kidney has occurred. Despite this limitation, change in creatinine remains the gold standard for the diagnosis of AKI. An evolution in the definition of AKI to better understand, characterize, and study the disease spectrum, has occurred, which has sought to capture the clinical importance of even small variations in kidney function. In addition, previous definitions used in the literature were widely disparate; this …

Caloric restriction ameliorates kidney ischaemia/reperfusion injury through PGC‐1α–eNOS pathway and enhanced autophagy

We investigated whether preconditioning with caloric restriction (CR) ameliorates kidney ischaemia/reperfusion (I/R) injury and whether the salutary effects of CR are mediated through enhanced autophagy and/or activation of key metabolic sensors SIRT1, AMP-kinase and PGC-1α. Six- to seven-week-old Wistar rats were divided into three groups: (i) sham-operated group; (ii) I/R group (40-min ischaemia followed by 24 h of reperfusion); and (iii) I/R group kept under CR (energy intake 70%) for 2 weeks before surgery. In additional experiments, sirtinol and 3-methyladenine (3-MA) were used as inhibitors of SIRT1 and autophagy respectively. Renal function was measured, and acute tubular damage and nitrotyrosine expression were scored. Kidney adenosine monophosphate-activated kinase (AMPK), SIRT1, eNOS, PGC-1α and LC-3B expressions were measured. Caloric restriction improved renal function, protected against the development of acute tubular necrosis and attenuated I/R-induced nitrosative stress. Kidney I/R injury decreased eNOS and PGC-1α expression, inhibit autophagy and increased SIRT1 and AMPK expressions by 2.6- and fourfold respectively. However, phosphorylation level of AMPK was decreased. As compared with I/R injury group, CR further increased kidney SIRT1 expression by 1.8-fold, promoted autophagy and counteracted I/R-induced decreases in the expression of eNOS and PGC-1α. 3-MA abolished the renoprotective effects of CR, whereas sirtinol did not influence renal function in CR rats with I/R injury. Caloric restriction ameliorates acute kidney I/R injury through enhanced autophagy and counteraction of I/R-induced decreases in the renal expression of eNOS and PGC-1α.

Rhabdomyolysis and Severe Muscle Weakness Secondary to Colistin Therapy

Rhabdomyolysis is a clinical condition that causes renal failure up to 40%. Rhabdomyolysis may be traumatic or nontraumatic. Colistin (polymyxin E) is an effective antibiotic. Nephrotoxicity is a frequently encountered side effect. The nephrotoxic effect of colistin is thought to be associated with increased membrane permeability, cell swelling and lysis, and the development of acute tubular necrosis. Here, we report a case of nontraumatic rhabdomyolysis associated with the use of colistin. There is only one report of rhabdomyolysis secondary to colistin in the literature, and there is no report of a case developing severe tetraparesis, as in our case.

Chapter 8. Hyperosmolar therapy

Chapter 8. Hyperosmolar therapy

Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review

Renal ischemia-reperfusion (I-R) contributes to the development of ischemic acute renal failure (ARF). Multi-factorial processes are involved in the development and progression of renal I-R injury with the generation of reactive oxygen species, nitric oxide and peroxynitrite, and the decline of antioxidant protection playing major roles, leading to dysfunction, injury, and death of the cells of the kidney. Renal inflammation, involving cytokine/adhesion molecule cascades with recruitment, activation, and diapedesis of circulating leukocytes is also implicated. Clinically, renal I-R occurs in a variety of medical and surgical settings and is responsible for the development of acute tubular necrosis (a characteristic feature of ischemic ARF), e.g., in renal transplantation where I-R of the kidney directly influences graft and patient survival. The cellular mechanisms involved in the development of renal I-R injury have been targeted by several pharmacological interventions. However, although showing promise in experimental models of renal I-R injury and ischemic ARF, they have not proved successful in the clinical setting (e.g., atrial natriuretic peptide, low-dose dopamine). This review highlights recent pharmacological developments, which have shown particular promise against experimental renal I-R injury and ischemic ARF, including novel antioxidants and antioxidant enzyme mimetics, nitric oxide and nitric oxide synthase inhibitors, erythropoietin, peroxisome-proliferator-activated receptor agonists, inhibitors of poly(ADP-ribose) polymerase, carbon monoxide-releasing molecules, statins, and adenosine. Novel approaches such as recent research involving combination therapies and the potential of non-pharmacological strategies are also considered.

Kuwait Experience in Laparoscopic Donor Nephrectomy: First 80 Cases

Introduction Laparoscopic donor nephrectomy (LDN) has been adopted rapidly as it offers less postoperative pain, early recovery, and better cosmetic results compared with the open approach. This prospective study investigated the results of the first 80 LDN performed between May 2005 and May 2006, with regard to donor morbidity and effect on graft function. Patients and Methods LDN was attempted in 80 donors by one surgical team. Donors included 68 men and 12 women, ages 22 to 53 years, with body mass indices of 17.9 to 42.4. According to computed tomographic angiography, left nephrectomy was planned in 75 donors and right nephrectomy in 5. Results LDN was completed successfully in 74 (92.5%) and converted to open in 6 (7.5%) secondary to technical difficulties and operative bleeding. The mean operating time for LDN was 186.16 minutes (range, 95–260 minutes). Mean warm ischemia time (WIT) was 5.7 minutes (range 2–16 minutes). Mean hospital stay was 5.28 days (range, 3–14 days). Two donors (2.5%) were reexplored for postoperative bleeding. Renal function in all donors was satisfactory within 3 months of surgery. Immediate diuresis occurred in 76 (95%) recipients. Acute cellular rejection was diagnosed in 1 recipient. No association was observed between WIT, graft function, development of acute tubular necrosis (ATN), or rejection. Plasma creatinine normalization was clearly associated with donor age. Conclusions LDN was found to be a safe procedure with low postoperative morbidity and short recovery time for donors. It can potentially increase the donor pool.

Acute tubulo-interstitial nephritis leading to acute renal failure following multiple hornet stings

BackgroundHornet stings are generally associated with local and occasionally anaphylactic reactions. Rarely systemic complications like acute renal failure can occur following multiple stings. Renal failure is usually due to development of acute tubular necrosis as a result of intravascular haemolysis, rhabdomyolysis or shock. Rarely it can be following development of acute tubulo-interstitial nephritis.Case presentationWe describe a young male, who was stung on face, head, shoulders and upper limbs by multiple hornets (Vespa orientalis). He developed acute renal failure as a result of acute tubulo-interstitial nephritis and responded to steroids.ConclusionRare causes of acute renal failure like tubulo-interstitial nephritis should be considered in a patient with persistent oliguria and azotemia following multiple hornet stings. Renal biopsy should be undertaken early, as institution of steroid therapy may help in recovery of renal function

PPAR alpha ligand protects during cisplatin-induced acute renal failure by preventing inhibition of renal FAO and PDC activity.

Previous studies demonstrated that during cisplatin-induced acute renal failure, there is a significant reduction in proximal tubule fatty acid oxidation. We now report on the effects of peroxisome proliferator-activated receptor-alpha (PPAR alpha) ligand Wy-14643 (WY) on the abnormalities of medium chain fatty acid oxidation and pyruvate dehydrogenase complex (PDC) activity in kidney tissue of cisplatin-treated mice. Cisplatin causes a significant reduction in mRNA levels and enzyme activity of mitochondrial medium chain acyl-CoA dehydrogenase (MCAD). PPAR alpha ligand WY ameliorated cisplatin-induced acute renal failure and prevented cisplatin-induced reduction of mRNA levels and enzyme activity of MCAD. In contrast, in cisplatin-treated PPAR alpha null mice, WY did not protect kidney function and did not reverse cisplatin-induced decreased expression of MCAD. Cisplatin inhibited renal PDC activity before the development of acute tubular necrosis, and PDC inhibition was reversed by pretreatment with PPAR alpha agonist WY. Cisplatin also induced increased mRNA and protein levels of pyruvate dehydrogenase kinase-4 (PDK4), and PPAR alpha ligand WY prevented cisplatin-induced increased expression of PDK4 protein levels in wild-type mice. We conclude that PPAR alpha agonists have therapeutic potential for cisplatin-induced acute renal failure. Use of PPAR alpha ligands prevents acute tubular necrosis by ameliorating cisplatin-induced inhibition of two distinct metabolic processes, MCAD-mediated fatty acid oxidation and PDC activity.

Potentiation of Gentamicin Nephrotoxicity in the Rat by Infusion of Aprotinin

The present study was undertaken to examine a possible effect of aprotinin, a 6.5-kDa polypeptide with an inhibitory effect on proteolysis, on aminoglycoside nephrotoxicity. Experimental animals (female Sprague-Dawley rats, 175-200 g body wt) were treated for 4 days with 40 mg/kg gentamicin given ip at 12-hr intervals. Aprotinin (40,000 kIU per animal) was infused iv over a period of 8 days, using subcutaneously implanted miniosmotic pumps. In protocol A, infusion pumps were placed 4 days before starting gentamicin treatment. In protocol B, pumps were implanted 15-18 hr prior to first gentamicin administration. In addition to rats exposed to both gentamicin and aprotinin (GAP), animals were treated with gentamicin ip + saline iv (G), saline ip + aprotinin iv (AP), or received only saline by both routes of administration (C). All rats were terminated 4 days after the end of gentamicin dosing. One hour before sacrifice, 200 μCi of [ 3H]thymidine was given ip to each animal in order to monitor cell turnover in renal tissue. The kidneys were analyzed with respect to (i) histopathological alterations and renal dysfunction, (ii) aminoglycoside tissue accumulation, and (iii) tubular regeneration (measurement of cell proliferation). In animals receiving aprotinin alone, histological examination of renal cortex on paraffin sections disclosed mild tubular injury with focal cell necrosis. In plastic-embedded tissue, proximal tubule epithelium was characterized by the presence of numerous inclusions densely stained with toluidine blue. At the ultrastructural level, these inclusions appeared filled with amorphous electron-dense material. In gentamicin-treated animals, cortical drug accumulation reached values higher than 0.3 mg/g renal tissue, but a significant 30-40% decrease of gentamicin accumulation was noted in GAP groups, compared to G groups. Histological examination of renal cortex (paraffin sections) revealed the development of acute tubular necrosis in both G and GAP groups. Tubular injury was accompanied by mild renal dysfunction, as shown by the level of serum creatinine which was increased almost 3-fold in the G group, compared to C and AP groups. Aprotinin infusion produced a further increase of serum creatinine, particularly in protocol A where it was 72% higher for the GAP group than for the G group. In both G and GAP groups, postnecrotic tubular regeneration was evidenced by determining the rate of DNA synthesis and the frequency of S-phase cells in renal cortex. Both methods gave consistent results and showed a 8- to 13-fold increase of cell proliferation in groups receiving gentamicin alone, compared to C groups. Furthermore, a significantly higher proliferative response was observed in GAP groups, in comparison with G groups. To conclude: (i) aprotinin alone induces in proximal tubule epithelium morphological abnormalities suggesting the accumulation of peptide-like material; (ii) aprotinin increases the severity of aminoglycoside-induced tubular necrosis (evaluated by the degree of tubular regeneration) and renal dysfunction (assessed by the measurement of serum creatinine).

Is there an optimal time for the first cyclosporin dose in renal transplantation?

Abstract It is customary for patients undergoing kidney transplantation to receive their first dose of cyclosporin either just before or during the transplant operation. This ensures the early establishment of good levels of immunosuppression but might depress early graft function and contribute towards the development of acute tubular necrosis. In a controlled clinical trial, we have studied the effects of withholding cyclosporin for 12 h in patients undergoing cadaveric renal transplantation. Consecutive adult recipients of a cadaveric renal transplant were randomised to receive their first dose of cyclosporin (lOmg/kg p.o.) 6h prior to transplant surgery or 12 h afterwards. All patients received azathioprine (1.5 mg/kg i. v.) and methylprednisolone (0.5 g i. v.) in addition during surgery. From the 2nd day onwards both groups were treated with an identical triple immunosuppressive regimen. The 27 patients who received their first dose of cyclosporin post-operatively had significantly better immediate and subsequent function than did the 26 patients who received their cyclosporin at the time of surgery. The delayed dosing was associated with improved graft survival and no increase in the frequency of rejection episodes. This regimen is recommended for all patients receiving triple therapy.

The use of perioperative Doppler ultrasound as a screening test for acute tubular necrosis.

For many years Doppler ultrasound has helped to identify the cause of renal allograft dysfunction. However, Doppler examinations were often performed after the onset of acute renal failure. In the present study we used Doppler ultrasound during grafting to follow changes in renovascular resistance. As early as 30 min after the renal artery had been unclamped, the calculated resistance index (RI) at the hilar part of the renal artery was significantly higher in the group of patients who developed acute tubular necrosis (ATN) than in the group of patients with early normalization of renal function (P = 0.05). This result did not correlate with raised cold and warm ischemia times and serum creatinine level on discharge in patients who presented with ATN. RI higher than 0.730 min after unclamping allows for an identification of those grafts at greater risk for the development of ATN and should be an indication for the early introduction of intensive therapy.

The management of acute renal failure

Acute renal failure (ARF) is an uncommon problem in most developed countries because of the low incidence of and usually prompt treatmenl~ for dehydrating and infectious illnesses. The majority of patients with ARF are likely to be seen in major centres with renal, neonatal, cardiothoracic or oncology units. Acute renal failure can be defined as a sudden decrease in renal function with disturbance of water and electrolyte homeostasis and retention of nitrogenous wastes. It is usually accompanied by oliguria (urine output < 1 ml/kg body weight/hr in the young child or 300 mls/m2/day in an adult) but occasionally patients may have polyuria. The reader is referred to more specialist texts for discussion on pathophysiology a'nd special considerations in the newborn. 1-5 Pre-renal Causes are those conditions which reduce perfusion to the kidneys. This is an important group to recognise because prompt treatment may prevent the development of acute tubular necrosis and established renal failure. In this situation a comparison of plasma and urine biochemistry may be helpful. In pre-renal failure the urine should have a high osmolality with a low sodium and high urea and creatinine content. The urine to plasma urea and creatinine ratios should be raised but are of little use in clinical practice. Evidence of oliguria with a raised plasma urea and creatinine level in a child'with nephrotic syndrome is one of the few indications for albumin infusions (1 g/ kg body weight using 20% salt poor albumin) combined with careful doses of frusemide (1-2mg/kg body weight).

Nephrotoxicity of metals: effects on plasma membrane function

Heavy metal effects on the kidney have been studied for decades in an effort to understand the underlying mechanisms of action. Despite these efforts, little specific information is available on the cellular or subcellular insults which lead to the development of acute tubular necrosis and subsequent renal failure. Although these metals are very diverse, it is not uncommon for all of them to produce the same sequence of morphological events when given in nephrotoxic doses. Further, the morphological changes seen often vary only slightly from those reported for other, non-metallic nephrotoxicants. A major item of interest would be a mechanistic explanation as to how a large variety of chemicals produce similar nephrotoxic events. The micropuncture and microdissection experiments during acute renal failure in the rat [l] yielded much important information concerning the tubular site of action of mercuric chloride. In nephrotoxic doses, mercuric chloride disrupted the structure and function of the straight part of the proximal tubule. Subsequent ultrastructural and histochemical studies by McDowell et al. [2] and Zalme et al. [3] defined more precisely the morphological sequence of events which occurred after a nephrotoxic dose of mercuric chloride. These studies showed that a loss of the brush border in the proximal tubular areas occurred relatively early followed by vacuolization of the endoplasmic reticulum, rounding and clumping of the mitochondria, and ultimately the onset of necrosis and cell sloughing. It is important to note that, as reported earlier, the primary events occurred in the pars recta of the proximal tubule when the

Assessment of Renal Viability by Phosphorus-31 Magnetic Resonance Spectroscopy

To assess the applicability of phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the analysis of renal transplant viability and preservation techniques with respect to pre-transplant ischemia, we studied two rat groups. Twenty-five rat kidneys were subjected to various time increments of warm ischemia (Group A), and 31P-MRS was performed on each kidney at time intervals of up to 72 hours during simple hypothermic storage. We correlated findings of 31P-MRS with simultaneous findings of electron microscopic (EM) ultrastructural viability parameters (in Group A) and subsequent survival and renal function in 30 rats (Group B) subjected to similar amounts of variable ischemia. Intracellular phosphorus metabolite levels were nondestructively monitored by 31P-MRS via spectral peaks of NAD, sugar monophosphates (SP), and inorganic phosphate (Pi).We concluded: 1) SP/Pi and NAD/Pi ratios decay in a time-dependent manner for both warm and cold ischemia, although this process is much slower during cold storage; 2) EM viability parameters correlate with the development of acute tubular necrosis (irreversible damage) versus nonviability (gross cell death) on a qualitative basis only; and 3) 31P-MRS enables a quantitative assessment of renal viability and ischemic renal damage and can predict the degree of acute tubular necrosis and post-ischemic renal function.31P-MRS is potentially a noninvasive, nondestructive method of assessing viability during simple hypothermic storage of the rat kidney. Preliminary evidence shows that this MRS method can be applied to human kidney viability studies for clinical renal transplantation and urologic research concerning renal preservation.

Diuretic use in critical care

Diuretics have found wide application in critical care medicine. The use of mannitol and loop diuretics in a variety of life-threatening disorders is reviewed. The combined venodilatory and natriuretic effects of bumetanide, furosemide and ethacrynic acid relieve congestive symptoms in pulmonary edema. Although commonly administered to prevent development of acute tubular necrosis or in varying stages of evolving disease, few data are available to demonstrate the efficacy of mannitol or loop diuretics. An approach to the oliguric patient with acute tubular necrosis is described. The dangers of hyponatremia are reviewed, and the rational use of loop diuretics and hypertonic saline is outlined. The 3 loop-active agents inhibit calcium reabsorption in the thick ascending limb of Henle's loop and therefore have proved useful in treating hypercalcemia. A practical approach to the diuretic-saline treatment of severe hypercalcemia is outlined. The kaliuretic effect of loop diuretics can be used to advantage in patients with acute or chronic hyperkalemia. A guide to such therapy is described.

CADAVERIC RENAL TRANSPLANTATION: AN ANALYSIS OF 65 CASES

65 patients with end-stage renal disease received seventy-six cadaveric kidney transplants between July 1, 1965, and June 30, 1968. 32 patients are still alive, including 22 patients at more than one year. Of the patients surviving more than a year (including 5 survivors from an earlier series), renal function is steady in 18 and deteriorating in 9; 14 have moderate-to-severe proteinuria. In the 33 fatal cases, sepsis was the most significant contributing factor, followed by ureteric leaks and vascular complications. The duration of peritoneal dialysis, length of " warm " ischæmia-time of the grafted kidney, development of acute tubular necrosis, and the number of blood-transfusions received did not affect kidney function or survival.