Laboratory tests of renal function

The kidneys are vital organs in the management of fluid balance, waste product removal, electrolyte homeostasis, acid–base balance and endocrine function. Waste products removed by the kidney include urea, uric acid, creatinine and other foreign products with similar physiochemical properties. Urea and uric acid are by products of protein metabolism and creatinine is generated by the metabolism of creatine compounds from muscle. The kidney regulates fluid and electrolyte balance through controlling the composition and volume of urine. In the proximal convoluted tubule and the loop of Henle, 90% of sodium, potassium, calcium and magnesium are reabsorbed. Acid–base balance is achieved by regulating the excretion of hydrogen ions and bicarbonate buffering. The kidney also has a number of endocrine functions including the production of renin and erythropoietin as well as hydroxylation of vitamin D. The kidneys receive 25% of cardiac output, generating 170–200 litres of ultrafiltrate per day. Urine output is approximately 1.5 litres per day, which is concentrated ultrafiltrate through selective reabsorption of solutes and water. In this article we will discuss tests frequently used to assess renal function.     

Laboratory tests of renal function

The human kidney provides essential regulatory and excretory functions. Body water content, plasma electrolyte composition and plasma pH are all under the regulatory control of the kidney. In addition, the kidney provides a path of excretion for blood-borne, water-soluble, low-molecular-weight compounds. These include the end-products of protein metabolism, such as urea and creatinine, as well as foreign compounds with similar physicochemical characteristics and their metabolites. Endocrine activity of the human kidney includes the secretion of the hormones erythropoietin and renin and the activation of vitamin D by hydroxylation to its 1,25-dihydroxycholecalciferol form. The renal blood flow is immense, constituting 25% of resting cardiac output. The glomeruli form 170–200 litres of ultrafiltrate per day and the selective reabsorption of water and solutes results in the final formation of approximately 1.5 litres of urine for excretion. Here, commonly used laboratory tests of renal function are discussed, including glomerular filtration rate (GFR), creatinine clearance, serum creatinine concentration estimation of GFR, novel markers of acute kidney injury (AKI), serum urea concentration, urinalysis, free water clearance and endocrine changes in renal disease. It must be noted, however, that these tests require a clinical assessment of the patient to allow meaningful interpretation.     

Laboratory tests of renal function

The human kidney provides essential regulatory and excretory functions. Body water content, plasma electrolyte composition and plasma pH are all under the regulatory control of the kidney. In addition, the kidney provides a path of excretion for blood-borne, water-soluble, low-molecular-weight compounds. These include the end-products of protein metabolism, such as urea and creatinine, as well as foreign compounds with similar physicochemical characteristics and their metabolites. Endocrine activity of the human kidney includes the secretion of the hormones erythropoietin and renin and the activation of vitamin D by hydroxylation to its 1,25-dihydroxycholecalciferol form. The renal blood flow is immense, constituting 25% of resting cardiac output. The glomeruli form 170–200 litres of ultrafiltrate per day and the selective reabsorption of water and solutes results in the final formation of approximately 1.5 litres of urine for excretion. Here, commonly used laboratory tests of renal function are discussed, including glomerular filtration rate (GFR), creatinine clearance, serum creatinine concentration estimation of GFR, cystatin C assay, serum urea concentration, urinalysis, free water clearance and endocrine changes in renal disease. It must be noted, however, that these tests require a clinical assessment of the patient to allow meaningful interpretation.     

Two new concepts that might lead to a wearable artificial kidney.

A wearable artificial kidney involving two novel components is proposed. It consists of a turbulent flow ultrafiltering shunt, which supplies 20 liters of ultrafiltrate per day to a disposable activated charcoal cartridge (where creatinine, uric acid, and other tightly bound solutes are adsorbed) and then to an artificial loop of Henle (where the urea is concentrated into 2 liters of ultrafiltrate per day and discarded) from which 18 liters of cleansed, rewarmed ultrafiltrate containing 87% of the glucose is returned to the patient.     

Preoperative assessment for patients with renal impairment

In health, the role of the kidneys includes regulation of crucial physiological variables such as blood pressure, acid–base, fluid and electrolyte balance, along with the clearance and excretion of drugs and waste products. The prevalence of chronic kidney disease is increasing, and may be attributed to an ageing population and increased incidence of chronic diseases such as diabetes and hypertension. Acute kidney injury is also increasingly recognized among hospitalized patients. It is imperative to understand and identify key features of renal impairment in a patient prior to the provision of anaesthesia, in order to minimize the risk of complications resulting in increased perioperative morbidity and mortality. This article aims to provide the context and structure for the preoperative assessment of patients with renal impairment irrespective of its cause.     

Fluid and electrolyte problems in renal dysfunction

Nephrons are the structural and functional units of the kidneys. The nephrons affect changes to blood plasma via filtration, reabsorption, secretion and excretion. Through these mechanisms the kidneys maintain homeostasis of electrolyte concentrations, fluid volume, osmolality and acid–base balance. In addition to the work of the nephrons, the kidneys have further roles in calcium homeostasis and synthesize the hormones erythropoietin and renin. Acute injury and chronic failure of the kidneys can impact on the kidneys ability to maintain homeostasis and manage fluids and electrolyte balance effectively. This poses challenges to the anaesthetist, perioperative physician and the intensivist in maintaining homeostasis and preventing further injury or damage to the kidneys following surgical or medical stresses. Derangement of electrolytes can be fatal. Recognition and prompt treatment of these abnormalities are essential.     

Kidney–lung cross-talk and acute kidney injury

There is a growing appreciation for the role that acute kidney injury (AKI) plays in the propagation of critical illness. In children, AKI is not only an independent predictor of morbidity and mortality, but is also associated with especially negative outcomes when concurrent with acute lung injury (ALI). Experimental data provide evidence that kidney–lung crosstalk occurs and can be bidirectionally deleterious, although details of the precise molecular mechanisms involved in the AKI–ALI interaction remain incomplete. Clinically, ALI, and the subsequent clinical interventions used to stabilize gas exchange, carry consequences for the homeostasis of kidney function. Meanwhile, AKI negatively affects lung physiology significantly by altering the homeostasis of fluid balance, acid–base balance, and vascular tone. Experimental AKI research supports an “endocrine” role for the kidney, triggering a cascade of extra-renal inflammatory responses affecting lung homeostasis. In this review, we will discuss the pathophysiology of kidney–lung crosstalk, the multiple pathways by which AKI affects kidney–lung homeostasis, and discuss how these phenomena may be unique in critically ill children. Understanding how AKI may affect a “balance of communication” that exists between the kidneys and the lungs is requisite when managing critically ill children, in whom imbalance is the norm.     

Fluid sequestration: an early indicator of mortality in acute pancreatitis

Complete daily intake and output charts were available for 218 patients with acute pancreatitis. The patients were divided into three groups according to the relation between fluid intake and output. In 105 patients in whom there was negligible fluid sequestration (daily output within 2 litres of intake) there were six deaths (5.8 per cent). In 69 patients the daily fluid intake exceeded the output by 2 litres or more but this imbalance lasted for 48 h or less; six patients died (8.7 per cent). The remaining 44 patients sequestered 2 litres or more of fluid per day for more than 48 h or until death. Thirty-eight patients in this group died (86.4 per cent). Fluid sequestration of 2 litres or more per day, and lasting longer than 48 h, is an accurate and simple predictor of mortality in acute pancreatitis. In this study it had a sensitivity of 76 per cent and a specificity of 96 per cent. The predictive value of a positive result was 86 per cent and of a negative result 93 per cent (efficiency 92 per cent).     

Capabilities of the Redyo Cartridge for Regeneration of Hernofiltrate

Capabilities of the Redy cartridge for hemofiltrate regeneration were tested. Electrolytes, creatinine, BUN, uric acid, acid-base, glucose, heparin, fluoride and amino acids were measured in the cartridge inflow and outflow (V = 70 ml/min) over a four-hour period. There was complete adsorption of potassium, calcium, magnesium, creatinine, BUN, uric acid, phosphate and heparin. Sodium ions, hydrogen ions, fluoride ions and possibly other trace elements are released by the cartridge. Amino acid absorption is almost complete if the amino acids are aromatic, have two or more N-atoms or if they have S-atoms. When using hemofiltrate after sorbent regeneration for reinfusion to the patient, one has to consider electrolyte substitution (i.e., K, Ca, Mg), sodium balance, trace element metabolism, acid-base problems, amino-acid profiles and ammonia overload.     

体外循环患者术后发生急性肾损伤的风险评估

目的 探讨体外循环心脏停搏手术后并发急性肾损伤（acute kidney injury,AKI）的肾脏危险因素以及不同肾小球滤过率估测值（estimated glomerular filtration rate,eGFR）水平与AKI发生率之间的关系.方法 回顾性分析793例行体外循环心脏手术成人患者的临床资料,分别统计患者术前及术后7d内血肌酐（SCr）值、术后尿量,评价有无AKI的发生.采用回归分析等统计学方法研究SCr、尿素氮（BUN）、尿酸（UA）、血尿、蛋白尿,肾脏影像学异常（包括B超、CT及ECT）等因素与AKI之间的关系.采用简化MDRD公式计算eGFR,探讨不同水平的eGFR与AKI发生率之间的关系.结果 体外循环心脏停搏术后7d内并发AKI者136例（占17.1％00）;术前蛋白尿、肾脏体积缩小或弥漫性改变,肾积水,血肌酐、尿素氮浓度增高,eGFR≤90 ml· min^-1·（1.73 m^2）^-1等因素与AKI的发生明显相关（P＜0.01）;eGFR≤90 ml·min^-1·（1.73 m^2）^-1时,术后AKI发生率升高,且二者之间呈负相关.Logistic回归分析结果显示术前蛋白尿,肾脏体积缩小或弥漫性改变,血肌酐浓度增高为术后并发AKI的独立危险因素.结论 体外循环心脏停搏术前肾脏损伤可导致术后并发AKI,临床工作中必须谨慎评估风险和认真防治.     

Preservation of 32 human kidneys by simple cold storage for more than 48 hours

Transplant centers are reluctant to use kidneys stored cold for more than 48 hours. During a 6-year interval we transplanted 32 kidneys preserved by intracellular electrolyte flushing that were stored cold for 48.2 to 61.4 hours. Of the recipients 91 per cent required dialysis within 1 week after transplantation. The mean serum creatinine nadir within 1 month was 3.0 mg. per dl. and graft survival at 1 month was 81 per cent. Short-term kidney graft function was not influenced significantly by the addition of magnesium sulfate to the flush solutions or by cyclosporin immunosuppression. The 1 and 2-year actuarial kidney graft survival rates were 72 and 58 per cent, respectively. The 1 and 2-year mean serum creatinine levels were 1.9 and 1.6 mg. per dl., respectively. Kidneys can be transplanted successfully after 48 hours of simple cold storage following flushing with an ice-cold intracellular electrolyte solution.     

Cloning and Expression of a Urate Oxidase and Creatinine Hydrolase Fusion Gene in Escherichia coli

Objective: To construct a plasmid containing a urate oxidase and creatinine hydrolase fusion gene and transform the plasmid into Escherichia coli to decompose uric acid and creatinine. Methods: According to the GenBank data for the urate oxidase gene, specific primers were designed to amplify and remove the stop codon for the urate oxidase gene. The gene was then ligated into the plasmid pMG36e to construct pMG36e-U. Then, using the GenBank database for the creatinine hydrolase gene, primers were designed to amplify the creatinine hydrolase gene. This gene was ligated into pMG36e-U to form pMG36e-U/C. Next, this construct was transformed into E. coli, which was confirmed by screening the recombinant E. coli and sodium dodecylsulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The engineered bacteria were cultured with a specific concentration of creatinine and uric acid for 24 h. Then, the concentrations of creatinine and uric acid in the culture fluid were measured. Results: The recombinant gene fragment was approximately 1.68 kb, and it contained the urate oxidase and creatinine hydrolase genes. The transformed E. coli expressed creatinine hydrolase and uric acid oxidase. The creatinine decomposition rate increased by 43.5%, and the uric acid decomposition rate increased by 42.32%. Conclusion: The constructed recombinant plasmid containing a fusion gene of creatinine hydrolase and uric acid oxidase was transformed into E. coli, and the enzymatic activities were expressed.     

Comparison of imported with locally retrieved kidneys preserved by intracellular electrolyte flushing followed by cold storage

Ice-cold intracellular electrolyte flushing followed by cold storage and economy air shipment is the cheapest method to share kidneys for transplantation. This study from 1 center compares 62 primary cadaver kidney grafts imported from other centers to 128 that were retrieved locally. Cold ischemia time was 36.4 plus or minus 8.6 hours (mean plus or minus standard deviation) in the imported group and 24.2 plus or minus 8.8 hours in the locally retrieved group. The significant increase in first week dialysis (71 versus 42 per cent) and 1-month serum creatinine nadirs (2.63 plus or minus 2.73 versus 1.78 plus or minus 1.04 mg./dl.) was explained by longer cold ischemia times in the imported kidney grafts. There were no significant differences between the 2 groups with respect to actuarial kidney graft survivals and serum creatinine levels at 1, 2 and 3 years. Intracellular electrolyte flushing followed by simple cold storage and air transportation provides kidney graft survivals and long-term kidney graft function at minimal expense when the kidneys are retrieved from beating-heart cadavers and have undergone minimal warm ischemia.     

Clinical assessment of renal function

The kidney carries out many key functions in the body, including the maintenance of fluid, acid–base and electrolyte homeostasis, the removal of nitrogenous waste, the production of erythropoietin, the hydroxylation of vitamin D and an important influence on regulation of blood pressure. This perhaps explains the increased risk of morbidity and mortality postoperatively in patients with acute or chronic renal impairment. Identification of these patients preoperatively allows the assessment of risk to both the kidneys and other organs. Protective measures can then be used in these patients with close monitoring to minimize poor outcomes. Clinical assessment of kidney function involves a thorough history and physical examination, with supplementary blood and radiological investigations.     

Effect of furosemide on dialysis requirement following cadaveric kidney transplantation

High doses of furosemide have been reported to reduce the requirement for dialysis following cadaveric kidney transplantation. Depending on recipient age, alternate cadaver kidney transplant recipients received infusions of 200 to 400 mg. furosemide just before restoration of renal circulation. All recipients received infusions of mannitol during the hour before renal revascularization. All 50 kidneys were preserved with intracellular electrolyte solutions. Mean cold storage times (33.4 plus or minus 11.4 hours for recipients given furosemide versus 35.7 plus or minus 12.3 hours for controls) were not significantly different between the 2 groups. There were no significant differences in first week dialysis requirement between recipients given furosemide and controls (75 versus 73 per cent, respectively), first day urine output (2.2 plus or minus 4.2 versus 1.0 plus or minus 0.81., respectively), 1-month serum creatinine nadirs (2.1 plus or minus 1.1 versus 1.9 plus or minus 1.1 mg . per dl., respectively) and 1-month function rate (92 versus 92 per cent, respectively). High doses of furosemide did not prevent significant acute tubular necrosis following human cadaveric kidney transplantation when the recipients also received infusions of mannitol.     

Intestinal dialysis in experimental animals

The effect of dialysis of the small and large intestine on serum urea and creatinine levels and on electrolyte and water balance was experimentally investigated in bilaterally nephrectomized miniature pigs. For experiments on the small intestine a segment of terminal ileum approximately one metre long was used. Colonic perfusion was carried out after creating a double-bore transverse colostomy. Potassium-free dialysis fluids were perfused through the isolated intestinal loops at a flow rate of 2 litres per hour. In no instance was intestinal dialysis successful in prolonging life, nor did it produce any effective fall in serum urea and creatinine levels. Colonic perfusion had some influence on hyperkalaemia but small intestinal perfusion was ineffective. Water balance and electrolyte changes were also studied. In conclusion it is emphasized that in the light of these experimental results intestinal dialysis is likely to be of very little clinical value.     

Laparoscopic removal of a gigantic non-functioning kidney via retroperitoneal access

Hugely dilated kidneys can sometimes present as abdominal masses. These kidneys are invariably non-functioning and are managed by nephrectomy.We describe a case of massive kidney containing 12.5 litres on fluid which was managed by retroperitoneoscopic nephrectomy. The patient was a 24-year-old male who presented with a huge abdominal mass, anorexia and weight loss. Laparoscopic surgery for such a large kidney has not been previously reported. We discuss salient features of the procedure and elaborate on the modifications required in the case of significantly enlarged kidneys. This revised version was published online in August 2006 with corrections to the Cover Date.     

Kidney–liver pathophysiological crosstalk: its characteristics and importance

International Urology and Nephrology - The kidney plays a crucial role in controlling the blood volume and pressure, electrolyte and acid–base balance, erythropoietin secretion, as well as...     

Rehabilitating role of glutathione ester on cisplatin induced nephrotoxicity

Cisplatin caused differential toxic effects on blood glucose and plasma urea, uric acid and creatinine levels. Cisplatin also showed an inhibitory effect on kidney marker enzymes like alkaline phosphatase, acid phosphatase, aspartate aminotransferase and alanine aminotransferase. However, administration of glutathione ester modulates the toxic side effect of cisplatin observed in kidney enzymes, and in blood parameters. It seems that glutathione ester plays an important role in protecting against the cisplatin induced nephrotoxicity by inhibiting the accumulation of platinum in kidneys.     

Serum and urinary uric acid in primary hyperparathyroidism

Serum and 24-h urinary uric acid were measured in 29 patients with primary hyperparathyroidism pre- and post-operatively. No significant difference was observed. A positive correlation was found between the ratios of urinary calcium/creatinine and urinary uric acid/creatinine pre-operatively but not after surgery. The serum uric acid level showed an increase from the first to the third day post-operatively and returned to normal within a week, but in patients undergoing other urological operations there was no post-operative increase. On a low calcium diet the level of serum uric acid was found to be increased. These findings suggest that primary hyperparathyroidism has some influence on uric acid metabolism.