Urinary N-acetyl-beta-D-glucosaminidase as an indicator of tubular damage in multiple myeloma.

In 34 patients with multiple myeloma we have studied urinary N-acetyl-beta-D-glucosaminidase (NAG) as an index of tubular injury and related it to urinary light chain excretion and serum creatinine. Our results confirm the association of light chain proteinuria with both tubular damage and global renal impairment, but show that not all light chains are nephrotoxic. Tubular damage occurs independently of global renal impairment. Clinically, urinary NAG appears to be a useful index of early tubular damage in multiple myeloma.

Tubular function in multiple myeloma.

In 42 myeloma patients our results confirm the association of light chain proteinuria and renal damage, but suggest that while the amount of light chain excreted is an important factor, only some light chains are nephrotoxic. The excretion of the proximal tubular cell lysosomal enzyme N acetyl B D glucosaminidase was a sensitive index of tubular injury, while the presence of low molecular weight proteinuria (Retinol Binding Protein and Lysozyme) was shown to indicate tubular dysfunction in a kidney sufficiently damaged to produce an impaired GFR. Isolated defects of distal tubular function (acid load response and concentrating ability) were rare. Such changes were seen mainly as part of global renal impairment and were usually associated with such specific pathophysiological conditions as plasma hyperviscosity or tubular crystal deposition. Hypercalcemia had a specific effect on the concentrating ability independent of any impairment of renal acidification.

Glomerulonephritis and IgA deficiency.

A mild self-limiting mesangial proliferative glomerulonephritis is described in 3 patients with selective IgA deficiency (less than 0.05 g/l). In all cases there was irregular thickening of peripheral glomerular capillary loops and paramesangial deposits. Arteriolar hyalinosis was present in two of the three cases. By direct immunofluorescence, and immunoperoxidase techniques in one case, IgM was present in the glomeruli and C3 was present in blood vessel walls. Secretory component was not detected in the glomeruli of any of the patients. The polyethylene glycol (PEG) precipitation immune complex assay was positive for IgM and IgG immune complexes in one patient and weakly positive for IgM immune complexes alone in another. The serum of one patient contained milk precipitins. All three patients had suffered from recurrent upper respiratory tract infections. It is suggested that the glomerular IgM immune complex deposition is related to the IgA deficiency and that, although the immune complexes may be a consequence of antibodies to dietary bovine proteins, this could be due to recurrent upper respiratory tract infections. This type of glomerulonephritis appears to resemble IgM associated glomerulonephritis in some aspects. Careful appraisal is required to establish if this association constitute a specific entity.

The cost of chronic dialysis in multiple myeloma.

The complications and costs of chronic dialysis in 4 patients with renal failure due to multiple myeloma are presented. In three patients the paraprotein responded to chemotherapy though without recovery of renal function. These three patients are alive after 18, 16 and 15 months of dialysis, the other dying after 7 months. Hospital admissions ranged from 26 to 74 days per year with infections accounting for 54 to 87% of admission days, 62.5% of which occurred during the first three months of dialysis treatment, with an incidence of 2.4 to 6.9 admissions episodes per year. An in-house audit of our chronic dialysis patients indicated that treatment of myeloma patients is 5-33% more expensive. The extra cost in such high risk patients is mostly due to the greater number and longer duration of hospital admissions for infection. The other extra costs (in decreasing value) of blood products, antibiotics and chemotherapy are relatively small in comparison to in-patient treatment.

Severe haemorrhage from a lumbar artery as a complication of percutaneous renal biopsy.

A patient is described with severe haemorrhage from a lumbar artery following percutaneous renal biopsy. The exact source of haemorrhage in this previously unreported complication proved difficult to locate even at surgical exploration.

Determination of copper and zinc in blood plasma by ion chromatography using a cobalt internal standard.

Ion chromatography was used to detect levels of copper and zinc in blood plasma from renal dialysis patients on continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis (HD). The developed method used cobalt as an internal standard and when combined with the standard additions method improved the overall precision of the results by between -0.3 and 6.0% and -0.8 and 5.7% for copper and zinc, respectively. The method was compared with inductively coupled plasma optical emission spectrometry (ICP-OES) and the results indicated no significant difference between the two methods with or without an internal standard. Without an internal standard, tcalc was 0.869 with a tcrit of 2.201 (n = 12, P = 0.05) and with an internal standard, tcalc was 0.189 compared to a tcrit of 2.201 (n = 12, P = 0.05). The copper and zinc levels in blood plasma in both dialysis groups were not significantly different to the copper and zinc levels in blood plasma of the control patients. A convenient method of analysis of trace elements in blood such as ion chromatography with UV/VIS detection is useful for determining whether inorganic elements may be disrupted in the body due to changes in the state of health.

Should patients with renal failure associated with myeloma be dialysed?

In a study of renal function in multiple myeloma seven patients presented with renal failure and three developed it 16-106 months after diagnosis. All were dialysed. Infection with dehydration was a precipitating factor in all seven cases of acute or acute on chronic renal failure. Of these, two patients recovered normal renal function and one other was left with permanent renal impairment but no longer required dialysis. Results from the seven patients with acute renal failure and for the three with more chronic features support the practice of dialysis for all patients who present with renal failure. Dialysis is not indicated for those patients with progressive myelomatous disease. The study showed no evidence that chemotherapy permitted recovery from established renal failure. The prognosis in this elderly group is heavily dependent on the presence of cardiovascular or other degenerative disease.

The importance of urinary immunoglobulin light chain isoelectric point (pI) in nephrotoxicity in multiple myeloma.

There is clinical and experimental evidence to imply that urinary immunoglobulin light chains are nephrotoxic yet some patients pass large amounts for years with little renal damage. Animal experiments suggest that a light chain is more nephrotoxic if it has a high isoelectric point (i.e. is cationic in relation to urine pH). We studied 23 patients with multiple myeloma, measuring light chain excretion rate, light chain isoelectric point (pI) and creatinine clearance. Light chain excretion rate was independent of light chain isoelectric point and did not correlate with creatinine clearance. Light chain isoelectric point correlated with creatinine clearance, suggesting that this characteristic may be an important determinant of the nephrotoxic effect of these immunoglobulin constituents.

Renal micropolyarteritis: a treatable condition.

A 10-year retrospective study of 36 patients is presented; the patients comprised 27 with renal micropolyarteritis nodosa (microPAN) and nine with Wegener's granulomatosis. At presentation, 29 patients had significant renal impairment (creatinine greater than 150 mumol/l), with 18 requiring dialysis at some time during their illness. Eighteen patients showed rapid recovery of renal function, a further two with apparently chronic renal failure recovered renal function after 4 months dialysis and continued immunosuppression. Seven patients required chronic dialysis. No benefit was shown for any particular immunosuppressive regime, with three patients recovering renal function (two initially on dialysis) without any immunosuppression. Prognosis was better than in previous published series, especially considering the elderly population (mean 52.9 years), with an 80% 1-year and a 64% 5-year survival.