Prerenal Azotemia Research Articles

Kidneys in chronic liver diseases

Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support.

Clinical characteristics of obstructive uropathy associated with rotavirus gastroenteritis in Japan

Rotavirus gastroenteritis is severe and often results in dehydration and pre-renal azotemia. However, we have encountered four children with acute obstructive uropathy associated with acute rotavirus gastroenteritis, and several similar cases have been reported. Therefore, the aim of the present study was to clarify the epidemiology and clinical features of acute obstructive uropathy associated with acute rotavirus gastroenteritis in Japanese children. We sent questionnaires to all members of the Japanese Society for Nephrology and all authors who had published case reports of this disease in Japan, inquiring about patient age at diagnosis, sex, the type of stones, laboratory data and other factors. 21 reported patients were evaluable, ranging from 0.4 to 3 years. The sex distribution showed a strong male prevalence. Oliguria had appeared about 7 days after the onset of gastroenteritis. Most of the patients showed hyperuricemia and hyponatremia. The stones consisted mainly of ammonium acid urate. The patients were discharged with normal renal function. Although obstructive uropathy associated with rotavirus gastroenteritis is very rare, this disease condition should be explored when anuria is refractory to sufficient fluid replacement therapy or when oliguria persists despite recovery of the gastrointestinal symptoms.

The fallacy of the BUN:creatinine ratio in critically ill patients

Acute kidney injury (AKI) is common in critically ill patients and is associated with a high mortality rate. Pre-renal azotemia, suggested by a high blood urea nitrogen to serum creatinine (BUN:Cr) ratio (BCR), has traditionally been associated with a better prognosis than other forms of AKI. Whether this pertains to critically ill patients is unknown. We conducted a retrospective observational study of two cohorts of critically ill patients admitted to a single center: a derivation cohort, in which AKI was diagnosed, and a larger validation cohort. We analyzed associations between BCR and clinical outcomes: mortality and renal replacement therapy (RRT). Patients in the derivation cohort (N = 1010) with BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was significantly associated with increased mortality and a lower likelihood of RRT in all patients, patients with AKI and patients at risk for AKI. Patients in the validation cohort (N = 10 228) with a BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was associated with increased mortality and a lower likelihood of RRT in all patients and in those at risk for AKI, BUN correlated with age and severity of illness. A BCR >20 is associated with increased mortality in critically ill patients. It is also associated with a lower likelihood of RRT, perhaps because of misinterpretation of the BCR. Clinicians should not use a BCR >20 to classify AKI in critically ill patients.

Evaluation of Urinary Variables as Diagnostic Indicators of Acute Kidney Injury in Egyptian Draft Horses Treated With Phenylbutazone Therapy

The present study was undertaken to evaluate the diagnostic significance of various urinary variables to detect acute kidney injury (AKI) in Egyptian draft horses treated with phenylbutazone (PBZ) therapy. Medical records of 52 draft horses, with a history of musculoskeletal painful conditions and treated frequently with various daily doses of injectable PBZ, were reviewed. Of those 52 horses, 38 were enrolled in this study. AKI was tentatively diagnosed based on thorough history and clinical findings and in conjunction with multiple biochemical screening tests. Accordingly, diseased horses were categorized into two main groups; the first group included 14 horses with prerenal azotemia, whereas the second group included 24 horses with renal azotemia. Biochemically, urinary malondialdehyde, urinary gamma-glutamyl transferase/creatinine (Cr) ratio, urinary protein/Cr ratio, urinary glucose, urinary sodium, fractional excretion of sodium, and renal failure index were significantly higher (P < .05) in horses of group 2 than those of group 1. However, values of urinary Cr, urine/plasma Cr ratio, urinary urea, and urine/plasma urea ratio were significantly decreased (P < .05) in horses of group 2. Analysis of receiver operating characteristic curve showed high sensitivity and specificity of most tested urinary variables as well as their derived indices for detection of AKI in diseased horses. Our findings suggest that the examined urinary variables as well as their ratios are helpful in documenting AKI associated with PBZ nephrotoxicity in Egyptian draft horses; however, their interpretation should be done in the light of the specific clinical setting and in conjunction with a thorough clinical and physical examination.

Acute Kidney Injury and Chronic Kidney Disease in Hospitalized Patients With Cirrhosis

BackgroundRenal dysfunction is a common and potentially life-threatening complication in hospitalized patients with cirrhosis.AimsTo determine the prevalence, cause, and outcome of patients with cirrhosis and acute kidney injury (AKI) and/or...

Renal Function and Heart Failure Treatment

A number of studies have demonstrated a linkage between renal dysfunction and adverse clinical outcomes in both acute and chronic heart failure.1–3 Heart failure treatments can affect renal function in a variety of ways, with decreased glomerular filtration rate (GFR) during treatment often denoting a poorer prognosis.4–6 Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce GFR through intrarenal mechanisms yet convey reduced rates of morbidity and mortality, presenting the hypothesis that the association between change in GFR and clinical outcomes depends on the factors that drive that change more than on GFR itself. In this issue of Circulation: Heart Failure , Testani et al7 present evidence that supports this hypothesis, showing that within the SOLVD (Studies of Left Ventricular Dysfunction) study, early reduction in GFR was associated with increased mortality within the placebo group but not in the enalapril group. It is reasonable to conclude that inhibiting the renin-angiotensin system (RAS) reduces GFR through a mechanism that does not convey an adverse prognosis. In evaluating new therapies, focus should be placed on clarifying the pathways through which agents influence renal function. Article see p 685 Within the SOLVD study, despite exclusion of patients with serum creatinine of >2.0 mg/dL, baseline renal impairment was associated with reduced survival.2,3 Patients randomized to enalapril showed slight, but statistically significant mean increases in serum creatinine during treatment relative to those receiving placebo.8,9 There exist a number of putative mechanisms whereby heart failure therapies may influence renal function. Diuretics may predispose to prerenal azotemia through intravascular volume depletion, excessive cardiac preload reduction, and a resulting reduction in cardiac output. Loop diuretics also induce intrarenal mechanisms for reducing GFR, principally through adenosine release and diminished glomerular blood flow …

Proximal Colonic Secretory Villous Adenoma Causing Diarrhea and Depletion Syndrome

Purpose: An 80-year-old Caucasian woman with hypertension and diverticulosis presented with exacerbation of chronic diarrhea, described as progressive, watery, nonbloody, and voluminous (>1 liter/day). The diarrhea persisted while fasting and sleeping, but was worse with oral intake. She denied pain, fever, nausea, vomiting, dietary changes, recent travel, or any new medications. Colonoscopy performed 5 months prior for similar symptoms showed a 12 mm ascending colon tubulovillous adenoma, which was incompletely resected. Random biopsies revealed a “mild nonspecific chronic colitis.” Loperamide was used for presumed microscopic colitis, with partial improvement. Results: The patient was lethargic, but afebrile with normal vital signs. Physical exam was otherwise unremarkable. Laboratory testing was remarkable for hypokalemia (2.7 mmol/L), acute kidney injury (Cr=1.7 mg/dL), metabolic acidosis, and hypoalbuminemia (2.5 g/dL). Leukocytosis was absent. Metabolic and infectious studies were unremarkable. Fecal calprotectin, fat, and elastase, as well as stool osmotic gap, were normal. Gastrin and VIP levels were within normal limits. Abdominal films and duodenal biopsies were unremarkable. Colonoscopy revealed a 3 cm x 2 cm ascending colon polypoid lesion; biopsies identified it as a villous adenoma. Terminal ileum and random colon biopsies were normal. Endoscopic mucosal resection was performed, completely removing the lesion. Pathology revealed focal areas of villi with abundant, clear mucin-filled goblet cells, suggestive of secretory villous adenoma. On follow-up, this patient had complete resolution of her diarrhea and depletion syndrome, off loperamide. Discussion: Secretory villous adenomas of the colon may cause a depletion syndrome characterized by dehydration, prerenal azotemia, hypokalemia, metabolic acidosis, obtundation, and rarely, death. Histologically the villous epithelia are enriched with abundant, atypical, hypersecretory, clear mucin-filled goblet cells, in contrast to non-secretory villous adenomas. The mechanism of diarrhea may be due to abnormal mucin and/or prostaglandin production. Definitive management is endoscopic or surgical resection. Prostaglandin inhibitors have also been described as temporizing treatment. Cases published to date describe secretory villous adenomas located only in the rectum and sigmoid colon. Conclusion: We report a first case of proximal colonic secretory villous adenoma with depletion syndrome that resolved with endoscopic mucosal resection. This diagnosis should be considered in the differential of subacute or chronic watery diarrhea. It also underscores the importance of thorough right-sided colonoscopic inspection, for all indications.

Is It Time to Evolve Past the Prerenal Azotemia versus Acute Tubular Necrosis Classification?

For more than 70 years, the cornerstone for the diagnosis and management of acute kidney injury (AKI) has been the paradigm wherein its etiologies have been broken down into categories of prerenal, intrinsic, and postrenal disease ([1][1]). With postrenal obstruction usually readily apparent, the

Diagnostic Value of Urinary Sodium, Chloride, Urea, and Flow

Up to 30% of hospitalized critically ill patients may have a rise in serum creatinine concentration. In addition to history and physical examination, there is diagnostic value in assessing urinary electrolytes, solute excretion, and urine flow in these patients. The correct interpretation of these urinary parameters can avoid unnecessary volume overload and mechanical ventilation, risk factors for increased mortality in patients with rising serum creatinine. The present article also discusses the role of arterial underfilling in causing prerenal azotemia in the presence of an increase in total body sodium and extracellular fluid expansion. As with extracellular fluid volume depletion, arterial underfilling secondary to impaired cardiac function or primary arterial vasodilation can delay or prevent recovery from ischemic or toxic acute tubular necrosis. The present brief review discusses the various aspects of the correct interpretation of urinary electrolytes, solute excretion, and urine flow in the setting of a rising serum creatinine concentration.

Acute Kidney Injury Associated with Hepato-protective Chinese Herb – Pien Tze Huang

The Chinese herbal formula, Pien Tze Huang, is popular in Asian countries and the United States for its hepato-protective effects. This report concerns two patients who took Pien Tze Huang, and who initially exhibited polyuria, followed by weight loss and an acute kidney injury. When the patients stopped taking Pien Tze Huang, and was given with intravenous normal saline, the renal function gradually recovered. The main component of Pien Tze Huang is Panax notoginseng that has a diuretic effect in animal studies. In the first patient, the patient received larger than the normal dosage. The possibility of heavy metal induced nephropathy was excluded by the history, and no aristocholic acid levels were detected in their blood. Besides, a normal renal biopsy excluded acute tubulo-interstitial injury. However, these two patients were diagnosed as having prolonged prerenal azotemia by a low percentage of fraction of sodium excretion in Patient 1, and a high urine gravity in Patient 2. We believed that we should be alert to any adverse effects of Chinese herbs, which are usually thought to be healthy and harmless to human body. The cautious usage of this kind of remedy and supervision by well-trained professionals are mandatory.

Outcomes following Dialysis for Acute Kidney Injury among Different Stages of Chronic Kidney Disease

Background: Information is limited regarding the outcomes of patients with preexisting chronic kidney disease (CKD) who develop dialysis-requiring acute kidney injury. Methods: 131 adult patients with advanced CKD who received emergent hemodialysis from January to June in 2002 were recruited and monitored for all-cause mortality and end-stage renal disease until the end of 2007. Results: Among patients investigated, 21 (16%) were successfully withdrawn from acute hemodialysis after an average of 8 sessions of dialysis therapy (range: 1–44). Multivariate analysis revealed that larger kidney size (odds ratio, OR = 1.755, p = 0.018), lower predialysis creatinine (OR = 0.722, p = 0.002), and non-diabetes (OR = 0.271, p = 0.037) were predictors for withdrawal. After 5 years, all patients in the non-withdrawal group remained on chronic dialysis, whereas only 8/21 (38%) patients in the withdrawal group developed end-stage renal disease. Cox’s analysis showed that age (hazard ratio, HR = 1.043, p < 0.0001), prerenal azotemia (HR = 1.040, p = 0.002), and adjusted propensity score for assigning to dialysis withdrawal (HR = 6.819, p = 0.008) were associated with mortality. Withdrawal from acute dialysis was not related to long-term mortality (p = 0.34). Conclusions: Among the advanced CKD patients, predictors of the successful weaning from acute dialysis were non-diabetes, larger kidney size and lower serum creatinine levels. The strategy of removal from emergent dialysis was not related to long-term mortality.

Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis

We have identified a novel homozygous nonsense mutation (W516X) in the kidney-type electrogenic sodium bicarbonate cotransporter 1 (NBC1) in a patient with isolated proximal renal tubular acidosis (pRTA). To specifically address the pathogenesis of this mutation, we created NBC1 W516X knock-in mice to match the patient's abnormalities. The expression of NBC1 mRNA and protein in the kidneys of NBC1(W516X/W516X) mice were virtually absent, indicating that nonsense-mediated mRNA decay (NMD) is involved in the defective transcription and translation of this mutation. These mice not only recapitulated the phenotypes of this patient with growth retardation, pRTA, and ocular abnormalities, but also showed anemia, volume depletion, prerenal azotemia, and several organ abnormalities, culminating in dehydration and renal failure with early lethality before weaning. In isolated renal proximal tubules, both NBC1 activity and the rate of bicarbonate absorption were markedly reduced. Unexpectedly, there was no compensatory increase in mRNA of distal acid/base transporters. Sodium bicarbonate but not saline administration to these mutant mice markedly prolonged their survival, decreased their protein catabolism and attenuated organ abnormalities. The prolonged survival time uncovered the development of corneal opacities due to corneal edema. Thus, NBC1(W516X/W516X) mice with pRTA represent an animal model for metabolic acidosis and may be useful for testing therapeutic inhibition of NMD in vivo.

Prerenal azotemia from excessive sweating in an adult with a cystic fibrosis gene mutation

We present the case of a 58-year-old male with chronic kidney disease who was admitted to the hospital multiple times with extracellular fluid volume depletion and prerenal azotemia. Some episodes were associated with gastrointestinal fluid losses and others with profuse diaphoresis in the absence of gastrointestinal fluid losses. At the age of 57 years, a common cystic fibrosis transmembrane conductance regulator protein mutation and a family history of cystic fibrosis were documented. We hypothesize that the abnormal cystic fibrosis transmembrane conductance regulator resulted in repeated bouts of excessive sweating, extracellular fluid volume depletion, and acute renal failure. This case is unique because of the prolonged period of time over which multiple documented episodes of prerenal acute renal failure occurred and because of the onset of the episodes in adulthood.

A patient with foot ulcer and severe metabolic alkalosis

We report a case of triple acid-base disorder with metabolic alkalosis as the primary disorder in a 65-year-old man due to ingestion and application to leg ulcers of baking soda (calcium bicarbonate). The blood pH was 7.65 with hypochloremia, hypokalemia, and prerenal azotemia. He was treated with isotonic saline with K replacement, and the patient improved without any adverse clinical consequences. We discuss the causes, mechanisms, and management of Cl-responsive (depletion) metabolic alkalosis.

Curbing the Use of Ultrasonography in the Diagnosis of Acute Kidney Injury: Penny Wise or Pound Foolish?

Curbing the Use of Ultrasonography in the Diagnosis of Acute Kidney Injury: Penny Wise or Pound Foolish?

Burr Red Blood Cells (BC) In Patients with Disseminated Intravascular Coagulation (DIC)

AbstractAbstract 5141Burr red blood cells (BC) in patients with disseminated intravascular coagulation (DIC). Background:Angiopathic hemolysis with schistocytes occurs in a minority of DIC patients. Burr cells (BC), are morphologically homogeneous, with a serrated membrane resembling that of red cells (RBC) in a hypertonic medium. They are associated with acute renal insufficiency, and have been observed in DIC. Methods:Criteria for patient inclusion were sepsis, often with multi-organ failure and hypotension. Of the 39 patients studied, 20 had DIC, based on platelet counts <100,000, and an International Society of Hemostasis and Thrombosis score of ≥5, derived from D-dimer or fibrin split product levels, prothrombin time elevations, and fibrinogen levels. The percentages of BC and schistocytes were determined by 1000 RBC counts, without knowledge of data concerning DIC. Patients' [Hb]'s, serum creatinine and blood urea nitrogen (BUN), were recorded. Results:Five of the 20 DIC patients succumbed to their acute illness, while 15 recovered without developing renal insufficiency. The BC%'s of the 20 DIC patients ranged from 0–80%, with a median of 18% and a mean of 27%; in the 19 patients without DIC the range was 0–45%, the median 6.4% and the mean 11% (p=0.046). The schistocyte percentages in patients with and without DIC ranged from 0.20–17, and 0–78; the respective medians and means were 1.1% and 1.0%, and 3.0–5.8%. The median and mean [Hb]'s of the patients with and without DIC were 9.3 and 11, and 9.6 and 10.3, respectively. BC% did not correlate with the [Hb]. The median creatinine levels of patients with and without DIC were 0.92 and 0.93 mg/dl, though the DIC patients' BUN's were higher (medians 31 vs 15). The BC% correlated with neither the BUN nor the BUN/creatinine ratio. The median and mean serum sodium levels in patients with and without DIC were 137. Conclusion:BC's are significantly more frequent in septic patients with DIC than in those without it. BC% did not correlate with anemia, implying that BC do not cause significant hemolysis, though there was a trend to lower [Hb] in the DIC patients. BC% was much higher than that of schistocytes in both groups, and schistocyte percentages did not correlate with DIC or BC%. Because of the DIC patients' higher BUN's and BUN/creatinine ratio's, we cannot exclude a role for the factors, which caused pre-renal azotemia in BC formation. BC formation may prove to be a criterion for DIC. Disclosures:No relevant conflicts of interest to declare.

Risk Factors for Recurrent Heart Failure Events in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT‐II)

Risk Factors for Recurrent Heart Failure. This study was designed to identify risk factors for recurrent heart failure (HF) events in patients with ischemic left ventricular dysfunction enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). The Prentice, Williams, and Peterson (PWP) statistical model was utilized to identify and compare risk factors for 1 or ≥ 2 HF hospitalizations among 1,218 patients with ischemic left ventricular dysfunction enrolled in the MADIT-II trial. Risk factors for a first HF hospitalization included treatment with an ICD (HR = 1.31; P = 0.05), New York Heart Association class > II (HR = 1.95; P < 0.001), female gender (HR = 1.38; P = 0.05), atrial fibrillation (HR = 1.90; P = 0.001), QRS >120 ms (HR = 1.41; P = 0.01), diabetes mellitus (HR = 1.51; P = 0.003), heart rate ≥ 80 (HR = 1.35; P = 0.04), diuretic therapy (HR = 1.82; P < 0.001), and the presence of prerenal azotemia (defined as blood urea nitrogen:creatinine > 20; HR = 1.45; P = 0.01). In contrast, prerenal azotemia was the only risk factor that was independently associated with a significant increase in the risk of ≥ 2 HF hospitalizations (HR = 1.52; P = 0.027). The occurrence of 1 HF event after enrollment was associated with a 2.8-fold (P < 0.001) increase in the risk of death, whereas after the occurrence of a second event there was a 6.7-fold (P < 0.001) increase in the risk of subsequent mortality. In MADIT-II, prerenal azotemia was the only significant and independent risk factor for HF progression after a first event, and recurrent HF was the most powerful predictor of mortality. These findings stress the importance of identifying risk factors for HF progression among patients who receive an ICD for primary prevention.

Defining prerenal azotemia in clinical practice and research

Prerenal azotemia is a common occurrence in hospitalized patients and is generally easier to define in clinical practice than in clinical research. Monitoring the duration of acute kidney injury and biomarkers of kidney function might help distinguish prerenal azotemia from acute tubular necrosis in both clinical practice and research settings.

Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia

While the fractional excretion of solutes have long been considered excellent research tools to investigate tubular physiology, their clinical use has become common over the last 40 years in the diagnoses of many disorders; however, none have reached the clinical utility of the fractional excretion of sodium in the ability to distinguish pre-renal azotemia from acute tubular necrosis. Nevertheless, there are many drugs and medical conditions that interfere with that utility and recently other solutes, including urea, uric acid and lithium, have been recently investigated to improve the diagnostic ability in clinical situations where the fractional excretion of sodium is known to be unreliable. We review the tubular physiology of these solutes and show how the differences in tubular physiology might be exploited to develop a strategy for their optimal clinical use.

Villous Adenoma of the Distal Sigmoid Colon Presenting with Chronic Diarrhea

Purpose: Villous adenomas account for 3-16% of adenomatous polyps. Although they represent a small percentage of neoplastic polyps, their malignant potential should not be minimized. Villous adenomas carry a high risk of progression to invasive carcinomas, and infiltrating carcinoma may be found in approximately 40% of tissue sampling with biopsy. Villous adenomas can manifest in three fashions: obstruction, electrolyte imbalance, or both. This is a case report that outlines the importance of villous adenomas as a part of the differential consideration when diarrhea and electrolyte depletion are presenting symptoms. Methods: A case study of a patient, conducted in 2010, who presented with severe electrolyte derangement, chronic watery diarrhea, hypotension and anemia. The history, hospital course, and supporting literature were evaluated and integrated into a case report. Results: Initial laboratory analysis demonstrated a hyperchloremic acidosis with hypokalemia despite aggressive replacement measures. He continued to have 8-10 loose stools per day. Stool analysis demonstrated no fecal leukocytes, C. difficile toxin A and B negative, occult blood trace positive and cultures negative for Salmonella, Shigella, Campylobacter or E. coli 0157. Seven days after admission, the patient underwent colonoscopy for evaluation of his chronic diarrhea and anemia which demonstrated a sessile 5 × 5 cm polyp in the distal sigmoid colon. Narrow band imaging suggested an adenomatous appearance. Biopsies confirmed it was a villous adenoma. Conclusion: It was in 1954 when McKittrick and Wheelock described a population of patients with profuse watery diarrhea with severe electrolyte disturbances most notably hyponatremia and hypokalemia were secondary to distal colon villous adenomas. This fluid and electrolyte loss accompanied by dehydration, circulatory collapse, prerenal azotemia and metabolic acidosis was labeled “depletion syndrome”. It is clear that the volume of diarrhea is directly correlated to the size of the tumor, the secreting surface area presented by innumerable papillary projections and activity of the surface cells. Successful management of this electrolyte derangement and diarrhea requires aggressive correction of fluid imbalance and that complete removal of the tumor with a margin of normal tissue is the only curative treatment.