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Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function.

A 39-year-old woman arrived to the emergency department complaining of a constant, progressive, left flank pain, with no beneficial effect from spasmolytic and nonsteroidal antiinflammatory drugs. Two years before, she suffered another episode of right flank pain and stranguria, but instrumental examinations (ultrasonography, urography) remained negative. Besides a mild tenderness in the left flank, physical examination was normal. Blood chemistry panel showed leukocytosis (17.2 x 10(3) mL, neutrophils 82.8%) and a slight increase of serum lactate dehydrogenase (LDH) (543 U/L versus 230 to 460 U/L). Urinanalysis showed a slight hemoglobinuria (0.5 mg/dL), and sediment contained some red cells and leukocytes. Diagnostic examinations (ultrasonography, computed tomography) showed a left renal nonhomogeneous space-occupying lesion, orientative for renal malignancy. She was transferred to the urology department and operated. Both intraoperatory and histological diagnosis was ischemic infarction and, after exclusion of all possible underlying causes, final diagnosis was idiopathic renal infarction. Diagnostic procedures and literature reports are discussed.

Nephrotoxicity of free hemoglobin (Hb) based blood substitutes still awaits full elucidation. Previous reports attributed Hb passage through the renal glomeruli to a tendency of the Hb tetramer to dissociate into dimers. Now it has become more evident that the Hb tetramer is able to extravasate. It appears that the electrical charge of proteins plays an important role, with electronegativity and a low isoelectric point favoring intravascular persistence. This effect was utilized in the development of an improved blood substitute, comprising Hb reacted with o-ATP and o-adenosine, to form an intra- and intermolecularly cross linked product, which is reduced with glutathione. The modification reagents possess the desired pharmacologic activities and produce an increase in the electronegative charges on the Hb surface. All Hb polymers and chemically modified tetramers present in this solution have a uniform electronegative charge, with a pl of 6.1-6.2. In this present study, unmodified bovine Hb and an improved blood substitute were used for the replacement of 40% of the total blood volume in rats. The nephrotoxic effect was investigated by the determination of urinary output, glomerular filtration rate (GFR), fractional excretion of sodium (FENa), potassium (FEK), and chloride (FECl), urine/plasma osmolality ratio, and urine N-acetyl-beta-D-glucosaminidase (NAG) level. The free Hb and non heme protein contents in the urine were analyzed by using isoelectric focusing and size exclusion liquid chromatography methods. The results indicate that unmodified Hb is nephrotoxic. An initially elevated urinary output was followed by a significant oliguria associated with decreased GFR, FEK, and FECl and elevated FENa and NAG. Severe hemoglobinuria was associated with proteinuria. Analysis of urine from unmodified Hb treated rats revealed the presence of Hb tetramers. Histopathological examination of the kidneys showed cytoplasmic vacuolization of proximal tubular epithelium. On the contrary, an improved blood substitute did not produce any nephrotoxic reactions. It was found that this Hb solution did not pass through the renal glomerular barrier and was not present in urine samples. In conclusion, such a chemical and pharmacological alteration of Hb molecules reduced their interaction with renal glomeruli and suspended nephrotoxicity.

This study compares the effects of polyethylene glycol (PEG) modified bovine hemoglobin on vascular half-life and renal function in rabbits to those of unmodified bovine hemoglobin. Renal function was assessed by the measurement of the glomerular filtration rate, urinalysis, blood chemistries, hemoglobin (Hb) excretion rates, and tissue histology. The influence of infusion rates on hemoglobin excretion rates and organ morphology was also examined. The mean half-life of unmodified bovine hemoglobin was 3.0 +/- 0.1 (mean +/- SEM) h, which was extended 14-fold to 43.2 +/- 1.7 h following PEG conjugation. The glomerular filtration rate, urinalysis, and blood chemistries were not greatly affected by either the unmodified bovine hemoglobin or the PEG modified bovine hemoglobin. However, unmodified bovine hemoglobin did demonstrate significant hemoglobinuria (Hb excretion levels in excess of 1.0% of the infused dose [p < 0.05]) at all infusion rates given while PEG modified bovine hemoglobin did not. In addition, histological examination by light microscopy indicated that the most severe morphological changes occurred in animals that received unmodified bovine hemoglobin. This data suggests that PEG modification of bovine hemoglobin significantly reduced some of the adverse effects of bovine hemoglobin on renal physiology and morphology.

Nephrotoxicity is a problem of hemoglobin solutions (HbS) that still awaits full elucidation and correction. Therefore, a study was conducted using five HbS with different characteristics to replace 1/3 of blood volume in five groups of rabbits. All HbS contained bovine Hb, 6.5 g/dl, dissolved into a balanced electrolyte solution. HbS-I was Hb incompletely purified of stromal phospholipids and environmental bacterial endotoxins, and uncrosslinked; HbS-II was pure Hb non crosslinked; HbS-III was completely purified and crosslinked; HbS-IV was like HbS-III, but with pH 8.4; and HbS-V was like HbS-III, with the addition of mannitol. The effects of blood replacement with these solutions were studied on: (a) PAH clearance (expression of renal plasma flow); (b) endogenous creatinine clearance (expression of glomerular filtration); (c) fractional excretion of sodium and (d) urine/plasma osmolarity (expressions of tubular function). Histological changes were assessed after 24 hours. Significant alterations were observed in decrescent order following the administration of HbS-I, -II and -III, while HbS-IV and -V were well tolerated. These results suggest that the nephrotoxicity of Hb solutions can be prevented by the following steps: (1) complete purification of Hb; (2) complete crosslinking; and (3) protection of the kidney by alkalinization of the urine and/or the addition of mannitol.

An animal model was developed to investigate the effect of extracorporeal shock wave lithotripsy (ESWL) on a normal kidney. Rabbits were treated with 3,000 shock waves at 18 kV to each kidney. Blood and urine samples were collected daily before and after shock wave treatment. Serum levels of hemoglobin, creatinine, lactic dehydrogenase (LDH), creatinine phosphokinase (CPK), and total protein were determined. Urine determination of volume, total protein, hemoglobin, and creatinine were also made. All kidneys, after sacrifice, were subjected to histologic analysis. The average pre-treatment creatinine clearance of our rabbits was 8.3 ml./min. After the treatment, a significant (p less than 0.01) reduction in creatinine clearance was noted for four days. The reduction was to 0.61 ml./min. on day one, 0.87 on day two, 1.04 on day three, and so forth. Urine hemoglobin rose significantly (p less than 0.01) for the first three days from 0.0 to 1.5 gm./dl. Histologic examination at seven days showed focal subcapsular hemorrhage, tubular dilation, and interstitial hemorrhage. Histologic evaluation at two months revealed focal interstitial fibrosis. In conclusion, this study reveals that shock waves to the kidney have short term physiologic effects on renal function and permanent focal histologic effects, which do not effect long term physiologic function. Further research on the effects of ESWL on renal function and structure could be facilitated with the use of this model.

Exercise induces profound changes in the renal haemodynamics and in electrolyte and protein excretion. Effective renal plasma flow is reduced during exercise. The reduction is related to the intensity of exercise and renal blood flow may fall to 25% of the resting value when strenuous work is performed. The combination of sympathetic nervous activity and the release of catecholamine substances is involved in this process. The reduction of renal blood flow during exercise produces a concomitant effect on the glomerular filtration rate, though the latter decreases relatively less than the former during exertion. However, the degree of hydration has an important influence on the glomerular filtration rate. An antidiuretic effect is observed during intense exercise. Changes in urine flow are dependent on the plasma antidiuretic hormone levels which are increased by intense exercise. Heavy exercise has an inhibitory effect on most electrolytes (Na, Cl, Ca, P). With potassium, however, most studies report that potassium excretion is not consistently affected by moderate to heavy exercise. Increased aldosterone production helps the body to maintain sodium by increasing its reabsorption from the filtered tubular fluid. Recent studies suggest that sympathetic stimulation may be involved during exercise. Strenuous work leads to an increased excretion of erythrocytes and leucocytes in urine. Cylindruria has been regularly found in postexercise urine in different sports. Postexercise proteinuria is a common phenomenon in humans. It seems to be directly related to the intensity of exercise, rather than to its duration. This excretion of proteins in urine is a transient state with a half-time of approximately 1 hour. Postexercise proteinuria has a pattern different from normal physiological proteinuria. Immunochemical techniques demonstrate that postexercise proteinuria is of the mixed glomerular-tubular type, the former being predominant. The increased clearance of plasma proteins suggests an increased glomerular permeability and a partial inhibition of tubular reabsorption of macromolecules. Haemoglobinuria and myoglobinuria may be observed under special exercise conditions. The degree of hydration appears to be important to reduce these abnormalities.