Persistent Azotemia Research Articles

Heavy-chain deposition disease associated with multiple myeloma: a case report

Heavy-chain deposition disease (HCDD) is a rare disorder characterized by the deposition of monoclonal immunoglobulin. Due to the disease's rarity and diagnostic challenges, its prognosis is generally poor. Herein, we report a case of successful treatment of HCDD coexisting with multiple myeloma. A 56-year-old man presented at an outpatient clinic with complaints of whole-body pain, edema, and dyspnea that had persisted for 2 weeks. Diagnostic tests confirmed nephrotic syndrome, hematuria, and progressive renal failure. Serum immunofixation electrophoresis identified the presence of IgG kappa paraprotein. A diagnosis of multiple myeloma was established following a bone marrow biopsy. A renal biopsy revealed antibodies specific to the heavy chains of IgG on immunofluorescence, and electron microscopy showed diffuse electron-dense "powdery" densities in the glomerular basement membrane. Based on these findings, the patient was diagnosed with both HCDD and multiple myeloma. Following the diagnosis, the patient immediately began anti-plasma cell therapy using bortezomib, lenalidomide, and dexamethasone. Intermittent hemodialysis was initiated due to persistent azotemia during the diagnostic process; however, renal function improved significantly after only 1 month of therapy, allowing the discontinuation of dialysis. Early intervention with anti-plasma cell therapy, such as bortezomib, is known to improve prognosis in the early stages of the disease. This case report is presented to enhance understanding of HCDD and underscore the importance of prompt diagnosis and treatment in managing this rare condition.

Long-term safety of dietary salt: A 5-year ProspEctive rAndomized bliNded and controlled stUdy in healThy aged cats (PEANUT study).

High-salt diets promote urine dilution and decrease urolithiasis risk. Prospectively evaluate the safety of chronic high dietary salt intake (randomized controlled trial). Twenty research colony neutered, healthy aged cats (11.5 years [10.0-11.6], median [interquartile range]). Healthy cats were randomized to control or high-salt dry diets (sodium: 1.02 ± 0.16 [mean, SD] and 3.26 ± 0.30 g/Mcal metabolizable energy [ME], respectively; chloride: 2.26 ± 0.33 and 5.71 ± 0.28 g/Mcal ME, respectively), fed for up to 60 months. Assessments included CBC, plasma biochemistry, urinalysis, glomerular filtration rate (GFR), blood pressure, renal and cardiac (conventional Doppler and 2-dimensional color tissue Doppler) imaging, annually. Cats that died or were euthanized underwent necropsy. Diet effects over time were evaluated with linear mixed models. Follow-up duration (median [Interquartile range]) was similar between the control (38.7 months [28.6-48.2]) and high-salt group (51.4 months [45.7-59.0]). Diet had no significant effect on changes in GFR, blood pressure, plasma creatinine concentration, end-diastolic left ventricular (LV) wall thicknesses, LV internal diameters, LV systolic function, left atrial size, or systolic and diastolic Doppler variables. One control cat developed hypertension. One high-salt group cat developed persistent azotemia. Serial plasma biochemistry and urine specific gravity suggested early chronic kidney disease in 4 nonazotemic cats (2 per group), consistent with necropsy findings. In healthy aged cats, a commercial veterinary diet containing 3.26 ± 0.30 g/Mcal ME sodium was safe with regard to renal and cardiac function for up to 5 years.

Complications and Comorbidities in Foals Undergoing Surgical Repair for Uroperitoneum

Surgical repair is frequently effective at resolving uroperitoneum in foals, though complications occur. Despite their occurrence, management strategies used to address these complications, and their impact on survival are not clearly defined. To better describe the complications following surgical correction of uroperitoneum and to document treatment strategies and outcomes after intervention, a multi-center retrospective case series was performed. Medical record data of foals undergoing surgical treatment for uroperitoneum were retrieved from three surgical centers, and cases identified with complications or comorbidities were reviewed. Long-term follow-up was obtained through owner contact. Of 45 foals with uroperitoneum, 13 (29%) had complications or comorbidities following surgical repair. Uroperitoneum recurred in 9 (20%) foals 12–264 hours after surgery. Foals with recurrence were managed medically with an indwelling urinary catheter, repeat celiotomy, or were euthanized. Other comorbidities following repair included sepsis and persistent azotemia. One horse developed cystic calculi 14 months later. Urinary catheters maintained for 3–7 days in combination with medical and surgical interventions successfully resolved uroperitoneum. The decision to debride bladder tear edges or the selection of suture material or pattern did not impact recurrence or survival. Six (67%) foals with recurrent uroperitoneum survived to hospital discharge; 86% survived if treatment was attempted. Four (80%) of cases treated for recurrent uroperitoneum were alive without active medical problems >2 years later. Despite recurrence, medical or surgical treatment of recurrent uroperitoneum enables short-term survival, and maintenance of long-term health. Indwelling urinary catheters should be considered in select cases with recurrent uroperitoneum.

The tubule pathology of septic acute kidney injury: a neglected area of research comes of age

Oxidant stress and compromised microcirculation underlie renal pathophysiology in septic acute kidney injury (AKI). Holthoff et al. report that resveratrol ameliorates these coupled abnormalities. They did not establish the primacy of either defect in septic AKI. However, tubule mitochondrial defects were recently reported to be involved in septic AKI pathogenesis, and resveratrol targets PGC-1α and respiratory enzymes. Together, these findings open new avenues for research into long-unresolved issues in the pathophysiology of septic AKI.

17 AN EVALUATION OF THE DONOR PROFILES AND OUTCOMES OF DONORS IN LIVING DONOR LIVER TRANSPLANT (LDLT)

Background: Liver transplant often results in hemodynamic and biochemical changes in the immediate postoperative period, often causing more concern. Aim: To study the pre-operative clinical profile, and the hematological and biochemical changes in the immediate postoperative period up to 7 days following deceased donor liver transplantation (DDLT) patients. Method: A detailed assessment of the patients’ pre-operative clinical diagnosis, the presence of comorbid illness and postoperative hematological, biochemical, microbiological, and clinical events was made between survivors and those who died. Various parameters were compared between 2 groups to understand the various factors that determined early postoperative outcome in DDLT patients. Result: A total of 26 patients, categorized into Group I – 18 patients (survivors) and Group II – 8 (mortality). There was no difference in the fluctuation of hemoglobin levels between the 2 groups (10% ± 4%). Early leukocytosis and persistent azotemia predicted early morbidity and mortality. A significant fall of platelet count predicted mortality. Transaminases showed a significant rise between the second and third postoperative days, stabilized and then showed downward trends between the seventh and ninth postoperative days in both groups. Hypernatremia predicated early mortality. Cause of death was due to intra-operative events such as cardiac arrhythmias, and due to ischemic cardiac events (2), pulmonary thromboembolism (1), and hepatic artery thrombosis (1), and sepsis and multiorgan failure (4). Two patients required renal replacement therapy for resistant renal failure in Group II. Conclusion: Pre-operative comorbid illness, postoperative worsening azotemia, persistent leukocytosis, and sepsis and cardiac events in the immediate postoperative period predict an outcome post-DDLT. is a very rare among such inherited disorders. Timely intervention and definitive treatment can change the prognosis in this group.

18 EARLY POSTOPERATIVE MORTALITY IN RECIPIENTS FOLLOWING DECEASED DONOR LIVER TRANSPLANTATION (DDLT)-A CLINICAL PROFILE

Background: Liver transplant often results in hemodynamic and biochemical changes in the immediate postoperative period, often causing more concern. Aim: To study the pre-operative clinical profile, and the hematological and biochemical changes in the immediate postoperative period up to 7 days following deceased donor liver transplantation (DDLT) patients. Method: A detailed assessment of the patients’ pre-operative clinical diagnosis, the presence of comorbid illness and postoperative hematological, biochemical, microbiological, and clinical events was made between survivors and those who died. Various parameters were compared between 2 groups to understand the various factors that determined early postoperative outcome in DDLT patients. Result: A total of 26 patients, categorized into Group I – 18 patients (survivors) and Group II – 8 (mortality). There was no difference in the fluctuation of hemoglobin levels between the 2 groups (10% ± 4%). Early leukocytosis and persistent azotemia predicted early morbidity and mortality. A significant fall of platelet count predicted mortality. Transaminases showed a significant rise between the second and third postoperative days, stabilized and then showed downward trends between the seventh and ninth postoperative days in both groups. Hypernatremia predicated early mortality. Cause of death was due to intra-operative events such as cardiac arrhythmias, and due to ischemic cardiac events (2), pulmonary thromboembolism (1), and hepatic artery thrombosis (1), and sepsis and multiorgan failure (4). Two patients required renal replacement therapy for resistant renal failure in Group II. Conclusion: Pre-operative comorbid illness, postoperative worsening azotemia, persistent leukocytosis, and sepsis and cardiac events in the immediate postoperative period predict an outcome post-DDLT. is a very rare among such inherited disorders. Timely intervention and definitive treatment can change the prognosis in this group.

Evaluation of Predictors of the Development of Azotemia in Cats

Chronic kidney disease (CKD) is a common condition in geriatric cats. Diagnosis is based on the development of persistent azotemia with inadequate urine concentrating ability. Biomarkers are sought for early identification. Clinical variables, urine concentrating ability, proteinuria, and N-acetyl-beta-D-glucosaminidase (NAG) index will be predictive of cats at risk of developing azotemia within 12 months. Client-owned nonazotemic geriatric (>or=9 years) cats. Prospective longitudinal cohort study monitoring a population of healthy nonazotemic geriatric cats every 6 months until development of azotemia, death, or the study end point (September 30, 2007). Multivariable logistic regression analysis was used to assess baseline clinical, biochemical, and urinalysis variables, urine protein to creatinine ratio (UP/C), urine albumin to creatinine (UA/C) ratio, and urinary NAG index as predictors of development of azotemia. One hundred and eighteen cats were recruited with a median age of 13 years. Ninety-five cats (80.5%) had been followed or reached the study end point by 12 months of which 30.5% (29/95) developed azotemia. Age, systolic blood pressure, plasma creatinine concentration, urine specific gravity, UP/C, UA/C, and NAG index were significantly associated with development of azotemia in the univariable analysis (P<or=.05). However, in the multivariable analysis, only plasma creatinine concentration with either UP/C (Model 1) or UA/C (Model 2) remained significant. This study demonstrates a high incidence of azotemia in a population of previously healthy geriatric cats. Proteinuria at presentation was significantly associated with development of azotemia although causal association cannot be inferred. Evaluation of NAG index offered no additional benefit.

Acute intrinsic renal failure in cats: 32 cases (1997–2004)

To determine patient demographics, clinicopathologic findings, and outcome associated with naturally acquired acute intrinsic renal failure (ARF) in cats. Retrospective case series. 32 cats with ARF. Cats were considered to have ARF if they had acute onset of clinical signs (< 7 days), serum creatinine concentration > 2.5 mg/dL (reference range, 0.8 to 2.3 mg/dL) and BUN > 35 mg/dL (reference range, 15 to 34 mg/dL) in conjunction with urine specific gravity < 1.025 or with anuria or increasing serum creatinine concentration despite fluid therapy and normal hydration status, and no signs of chronic renal disease. Cases were excluded if cats had renal calculi or renal neoplasia. Causes of ARF included nephrotoxins (n = 18 cats), ischemia (4), and other causes (10). Eighteen cats were oliguric. For each unit (mEq/L) increase in initial potassium concentration, there was a 57% decrease in chance of survival. Low serum albumin or bicarbonate concentration at initial diagnosis was a negative prognostic indicator for survival. Initial concentrations of BUN, serum creatinine, and other variables were not prognostic. Seventeen (53%) cats survived, of which 8 cats had resolution of azotemia and 9 cats were discharged from the hospital with persistent azotemia. Results suggested that survival rates of cats with ARF were similar to survival rates in dogs and that residual renal damage persisted in approximately half of cats surviving the initial hospitalization.

Risk factors associated with renal insufficiency in horses with primary gastrointestinal disease: 26 cases (2000–2003)

To identify factors associated with renal insufficiency in colic- or colitis-affected horses with high serum creatinine (SCr) concentrations evaluated at a referral hospital. Retrospective case series. 167 colic- or colitis-affected horses (88 represented a random sample [hospital population], and 79 had high SCr concentration at initial evaluation [study population]). Medical records were reviewed. Data collected included signalment; physical examination, clinicopathologic, and diagnostic findings; and outcome. The study population was categorized on the basis of whether SCr concentration did (AR group; n = 53) or did not (PA group; 26) normalize within 72 hours of fluid therapy. Characteristics of the study and hospital populations were compared. Males and Quarter Horses were significantly overrepresented in the study population. Compared with the hospital population, study-population horses were significantly more likely to have colitis, gastric reflux, and diarrhea at initial evaluation. Initial mean SCr concentration in the PA group was significantly higher than the AR group; identification of gastric reflux, abnormal rectal examination findings, and hypochloremia were significantly associated with persistent azotemia after 72 hours of fluid therapy. Compared with the AR group, PA group horses were 3 times as likely to die or be euthanized. In colic- or colitis-affected horses, factors associated with renal insufficiency included gastric reflux, abnormal rectal examination findings, or hypochloremia initially; prognosis for horses in which azotemia resolves within 72 hours of treatment appears to be better than for horses with persistent azotemia.

Clinical disease and laboratory abnormalities in free-ranging desert tortoises in California (1990-1995).

Desert tortoise (Gopherus agassizii) populations have experienced precipitous declines resulting from the cumulative impact of habitat loss and human and disease-related mortality. Diagnosis of disease in live, free-ranging tortoises is facilitated by evaluation of clinical signs and laboratory test results but may be complicated by seasonal and environmental effects. The goals of this study were: 1) to describe and monitor clinical and laboratory signs of disease in adult, free-ranging desert tortoises at three sites in the Mojave Desert of California (USA) between October 1990 and October 1995; 2) to evaluate associations between clinical signs and hematologic, biochemical, serologic, and microbiologic test results; 3) to characterize disease patterns by site, season, and sex; and 4) to assess the utility of diagnostic tests in predicting morbidity and mortality. Venous blood samples were obtained four times per year from tortoises of both sexes at the Desert Tortoise Research Natural Area (DTNA), Goffs/Fenner Valley, and Ivanpah Valley. Tortoises were given a physical examination, and clinical abnormalities were graded by type and severity. Of 108 tortoises, 68.5% had clinical signs of upper respiratory tract disease consistent with mycoplasmosis at least once during the study period. In addition, 48.1% developed moderate to severe shell lesions consistent with cutaneous dyskeratosis. Ulcerated or plaque-like oral lesions were noted on single occasions in 23% of tortoises at Goffs and 6% of tortoises at Ivanpah. Tortoises with oral lesions were significantly more likely than tortoises without lesions to have positive nasal cultures for Mycoplasma agassizii (P = 0.001) and to be dehydrated (P = 0.0007). Nine tortoises had marked azotemia (blood urea nitrogen [BUN] > 100 mg/dl) or persistent azotemia (BUN 63-76 mg/dl); four of these died, three of which had necropsy confirmation of urinary tract disease. Laboratory tests had low sensitivity but high specificity in assessing morbidity and mortality; there was marked discrepancy between serologic and culture results for M. agassizii. Compared with tortoises at other sites, tortoises at DTNA were more likely to be seropositive for M. agassizii. Tortoises at Goffs were significantly more likely to have moderate to severe shell disease, oral lesions, positive nasal cultures for M. agassizii, and increased plasma aspartate aminotransferase activity. The severe disease prevalence in Goffs tortoises likely contributed to the population decline that occurred during and subsequent to this study.

Propylene Glycol Toxicity Associated with Lorazepam Infusion in a Patient Receiving Continuous Veno-Venous Hemofiltration with Dialysis

Propylene Glycol Toxicity Associated with Lorazepam Infusion in a Patient Receiving Continuous Veno-Venous Hemofiltration with Dialysis

THE USE OF 2 IPSILATERAL URETERAL STENTS FOR RELIEF OF URETERAL OBSTRUCTION FROM EXTRINSIC COMPRESSION

Purpose We present our early experience with the novel approach of placing 2 parallel stents simultaneously in extrinsically obstructed ureters in which single stents had failed. The increased stiffness of 2 stents reduces kinking and luminal compression, and the potential space between the stents likely preserves flow around as well as through them. Materials and Methods Four patients recently presented with ureteral obstruction secondary to nonurinary tract malignancies. Previous stenting with a single 6F Double-J * * Medical Engineering Corp., New York, New York. stent had failed in all cases. Three patients experienced flank pain and 1 had persistent azotemia within 3 days of initial stent placement. All patients had significant residual sonographic hydronephrosis despite good stent position. In all cases cystoscopy/stent exchange was performed under local anesthesia with intravenous sedation. Parallel 4.7F Double-J stents were placed simultaneously over 2, 0.035 hydrophilic coated glide wires under fluoroscopic guidance after removal of the malfunctioning 6F stent. Results Stent placement was uneventful in all 4 patients with prompt drainage of contrast material seen after parallel ipsilateral stent placement. Patients tolerated the double 4.7F parallel stents with no discernible difference in irritative symptoms compared to single 6F stents. Flank pain and azotemia resolved in 3 patients, and hydronephrosis improved in all 4 after placement of parallel Double-J stents. All patients remain alive with a mean followup of 5.8 months (range 4 to 8). Except for 1 patient who later underwent ureterolysis, each had subsequently had the stent changed every 3 months. No patient has required proximal urinary diversion (that is percutaneous nephrostomy tube). Conclusions Placement of 2 ipsilateral parallel ureteral stents simultaneously is an easy technique. It may obviate percutaneous nephrostomy tube placement in patients in whom drainage with a single stent failed, especially in cases of extrinsic ureteral compression.

Acquired immunodeficiency syndrome-associated renal disease in children.

Five children with acquired immunodeficiency syndrome (AIDS) and clinically significant renal disease had detailed pathologic examination of renal tissue (biopsy specimens, autopsy specimens, or both). All patients had proteinuria, hypoalbuminemia, and edema; one patient had persistent azotemia. In two cases, renal disease was the first manifestation of human immunodeficiency virus (HIV) infection. All patients had progressive renal disease, and four of the five died. Pathologic studies revealed focal glomerulosclerosis and mesangial proliferative glomerulonephritis with deposits of immunoglobulins and complement demonstrated by immunofluorescence and electron microscopy. Characteristic tubuloreticular structures were also demonstrated in the glomerular endothelial or epithelial cells in two cases. Renal disease is part of the multisystem involvement in children with AIDS. The pathogenesis of renal disease is not known, but circulating immune complexes are known to occur in children with HIV infection and may be involved.

Renal handling of urea in subjects with persistent azotemia and normal renal function

Fourteen subjects with persistent azotemia and normal glomerular filtration rate were studied by renal clearances and hormonal determinations to establish the nephron site of altered urea transport and the mechanism(s) responsible for their azotemia. During constant alimentary protein, urea nitrogen appearance was normal and urea clearance was much lower than in 10 age-matched control subjects (23.3 +/- 2.1 ml/min and 49.6 +/- 2.6 ml/min per 1.73 m2, P less than 0.001). Inulin and para-aminohippurate clearances, blood volume and plasma concentration of antidiuretic hormone were within normal limits. During maximal antidiuresis, in spite of greater urea filtered load, the urinary excretion of urea was less, and both the maximum urinary osmolality and the free-water reabsorption relative to osmolar clearance per unit of GFR were greater than in control subjects. After sustained water diuresis, the plasma urea concentration markedly decreased to near normal levels in azotemic subjects. The basal urinary excretion of prostaglandins E2 was significantly reduced in azotemic subjects and was directly correlated with fractional urea clearance (r = 0.857, P less than 0.001). An additional group of control subjects (N = 8) showed a marked reduction of fractional clearance of urea after inhibition of prostaglandin synthesis (P less than 0.01). These data suggest that azotemia is due to increased tubular reabsorption of urea in the distal part of nephron, presumably because of increased back diffusion in the papillary collecting duct, accounting for the enhanced maximum urinary osmolality and free-water reabsorption. Renal prostaglandin E2 may participate in the pathogenesis of azotemia by altering recycling of urea in the medulla.

Phase II trial of streptozotocin, mitomycin-C and 5-fluorouracil (SMF) in the treatment of advanced pancreatic cancer.

Ten of 23 patients with advanced measureable adenocarcinoma of the pancreas achieved an objective response after treatment with a regimen consisting of streptozotocin, mitomycin-C and 5-fluorouracil (SMF). The median duration of response is in excess of 7 months and responding patients have lived significantly longer than patients with progressive disease (7.5 + months vs. 3 months). The SMF regimen was adequately tolerated. Principal toxicities included myelosuppression, which was generally mild, nausea and vomiting. There was reversible nephrotoxicity in the form of proteinuria in 30% of patients and persistent axotemia in 9% of patients.

The Preponderance of Males in the Idiopathic Nephrotic Syndrome of Childhood

In this communication we will limit the discussion to children or adults who have massive proteinuria, hyperlipemia, and hypoalbuminemia occurring initially in the absence of preceding and persistent azotemia, hypertension, or decreased renal function and not in association with any recognized inciting agent or pre-existing systemic disease. It is considered distinct from the nephrotic syndrome (NS) occurring in the course of other renal diseases caused by chemical agents or in association with systemic diseases such as lupus erythematosus and other collagen diseases, amyloidosis or diabetes mellitus.

Pacemaker in Cardiac Vein

To the Editor:— The report by Mullen et al of two cases of cardiac tamponade from ventricular perforation by a transvenous pacemaker ( 203 :142, 1968) brought to mind a bizarre complication from this procedure which occurred last year at the Meadowbrook Hospital, East Meadow, NY. The patient was a 75-year-old man with chronic congestive heart failure and parkinsonism who entered the hospital with complete heart block. Preliminary management with an external pacemaker was followed one month later by subcutaneous implantation of a fixed rate pacemaker, the endocardial electrode in both instances being inserted via the right external jugular vein. Complete ventricular capture was recorded, and the rate remained at 78 to 80 beats per minute. However, increasing confusion and drowsiness were noted along with a mild, persistent azotemia. A gradual deterioration ensued, and the patient died after two months in the hospital. Autopsy showed advanced arteriosclerotic heart disease, acute bronchopneumonia