Leptospiral Acute Renal Failure: Effects of Dopamine and Furosemide

Abstract

From unpublished experience of clinicians in the rural tropics, the combination of furosemide and dopamine is beneficial in the management of mild acute renal failure in tropical disease. We studied two groups of patients with leptospirosis and mild acute renal failure whose serum creatinine ranged from 2.4 to 5 mg/dL and fractional excretion of sodium varied from 1.21 to 2.08%. Group 1, consisting of 9 patients with the serum creatinine ranging from 2.4 to 5 mg/dL, served as the control. They received only penicillin G sodium and supportive treatment. Group 2, consisting of 8 patients with the serum creatinine ranging from 2.8 to 5 mg/dL, received, in addition to penicillin, dopamine (renal dose) and furosemide along with fluid and electrolyte replacement. The control group ran the usual clinical course of acute renal failure, and 3 patients required dialysis. There was profuse diuresis, and the recovery of renal function was faster in group 2 patients. Dopamine and furosemide are therefore useful in mild acute renal failure in leptospirosis. It is felt that this combination could be beneficial in the management of mild acute ischemic renal failure due to a clean single insult.

Keywords:

• renal failure
• leptospirosis
• dopamine
• furosemide

INTRODUCTION

It is generally agreed that dopamine in combination with furosemide offers no beneficial effect in severe acute renal failure. Yet, the combination of dopamine and furosemide is often used by clinicians in the rural tropics in the management of mild acute rural failure, especially due to tropical diseases, with favorable results. Increased urine flow and the rapid improvement of renal function are observed. In a previous study of patients with falciparum malaria, dopamine and furosemide attenuated the progression of mild renal failure[1] but failed to prevent the progression of moderate and severe renal failure. The experience with tropical disease conflicts with the concept that dopamine and its combination with furosemide offer no benefit in the early stage of acute renal failure.[2–4] This could reflect the difference of the patients under study with respect to the clinical setting and the nature and severity of the disease. Clinically, acute renal failure is usually caused by multiple factors. The question should be answered by a study of renal failure due to a single disease. In this report, mild acute renal failure due to leptospirosis was chosen as a model to study the effects of dopamine and furosemide.

PATIENTS AND METHOD

A study was made in 17 patients with leptospirosis in mild renal failure. The patients entered the hospital 3–5 days after the onset of illness. Leptospirosis was serologically diagnosed by the standard microagglutination test.[5] The serum creatinine ranged from 2.4 to 5.0 mg/dL; blood urea nitrogen from 42 to 103 mg/dL; fractional excretion of sodium (FE_Na) from 1.21 to 2.08%; and total serum bilirubin from 3.9 to 9 mg/dL. The patients were divided into two groups. The clinical data are shown in Table 1. Both groups were comparable both in blood chemistry and age.

Table 1 Showing the clinical profile of the patients

Age (year)		BUN (mg/dL)		Scr (mg/dL)		Total bilirubin (mg/dL)		FENa (%)
G1	G2	G1	G2	G1	G2	G1	G2	G1	G2
35	28	42	68	2.4	2.8	3.9	4.1	1.21	1.39
32	41	95	103	4.8	5.0	5.9	4.2	1.53	1.75
40	32	60	54	2.8	3.0	6.2	5.8	1.32	1.44
27	44	64	62	3.2	3.2	9.0	8.1	1.46	2.08
24	26	88	92	4.4	4.4	5.2	6.1	1.69	1.84
26	30	72	78	3.8	3.9	7.5	9.2	1.88	1.67
37	22	80	82	3.9	4.0	4.4	7.4	1.37	1.48
42	34	84	76	4.2	4.2	4.8	5.4	1.78	1.98
31		98		5.0		6.8		2.01
32.7 ± 6.3	32.4 ± 6.6	75.9 ± 18.2	76.9 ± 15.9	3.8 ± 0.9	3.8 ± 0.8	6.0 ± 1.6	6.3 ± 1.8	1.58 ± 0.27	1.70 ± 0.25

Abbreviations: G1 = group 1; G2 = group 2; Sc_r = serum creatinine; FE_Na = fractional excretion of sodium.

Group 1

Nine patients served as control. Their serum creatinine ranged from 2.4 to 5 mg/dL, and the urine volume on the first hospital day varied from 310 to 620 ml. They received intravenous penicillin G sodium (1.5 million units 6 hourly) for a period of seven days along with intravenous fluid to maintain fluid balance.

Group 2

There were eight patients in this group. The serum creatinine varied from 2.8 to 5 mg/dL, and the urine flow on the first admission day ranged from 250 to 600 ml. They also received, in addition to penicillin as group 1, intravenous dopamine (3 μg/kg/min) and furosemide (200 mg 6 hourly) for 24 to 36 hours. Intravenous fluid with electrolytes was administered to match the urine flow and electrolyte loss.

Blood urea nitrogen, serum creatinine, and electrolyte and urine volume were daily measured in both groups.

RESULTS

Group 1

In all patients, the serum creatinine continued to rise. The clinical course was that of acute tubular necrosis. Three patients had serum creatinine above 7 mg/dL on days 6–8 and required hemodialysis. The serum creatinine in the remaining six patients returned to the normal level on the 18^th hospital day (see Figure 1). None of the patients in this group developed acute respiratory distress syndrome in the clinical course.

Figure 1. Graphic plots of the mean daily serum creatinine.

Group 2

There was profuse diuresis with the urine flow ranging from 3 to 5 liters/day and a decrease in serum creatinine. In five patients, the serum creatinine level was below 2 mg/dL on the sixth hospital day. On the 11^th hospital day, all patients had the normal serum creatinine (see Figure 1). The difference between the two groups is statistically significant (p < 0.002). No disadvantageous effects of dopamine were observed. The clinical course was uneventful.

DISCUSSION

All patients had mild renal failure based on the serum creatinine level and fractional excretion of sodium (FE_Na of 1–2%). A FE_Na of this magnitude is borderline between pre-renal and renal failure by the standard diagnostic criteria.[6] In leptospirosis, Na-K ATPase activity is inhibited by the bacterial outer membrane protein.[7] Tubular reabsorption of Na is decreased. Therefore, renal failure in leptospirosis with the FE_Na between 1 and 2% could even be pre-renal. Nevertheless, the difference in the clinical course of the two groups of patients is striking. In the control group, the serum creatinine continued to increase and took longer to return to normal. Three patients progressed to severe renal failure requiring hemodialysis. The disease ran the usual clinical course of leptospiral acute renal failure in the control group.[8] The findings suggest the ongoing progression of impairment of renal function in leptospirosis despite antibiotic therapy. Dopamine and furosemide given to group 2 patients induced diuresis and rapid return of the serum creatinine to normal.

Hemodynamically, in leptospirosis, the systemic vascular resistance is decreased while renal vascular resistance is increased,[9] and there is relative hypovolemia. In response, plasma arginine vasopressin, angiotensin II, and aldosterone are increased, which result in decreased renal blood flow, decreased GFR, and salt and water retention.[8],[9] This is similar to the findings in malaria.[10] At the clinical level, there may be subclinical hypotension or clinical hypotension when the disease is severe.[11] A decreased response to fluid load has been observed. This trade-off is a compensatory mechanism, which can be so intense to result in acute renal failure. Changes in glomerular filtration rate and renal blood flow depend on the severity of the disease. Based on the presence of jaundice and impaired renal function, the disease in these patients was considered severe. Switching off the compensating mechanism by volume expansion alone can be dangerous for fluid overload because of the decreased response to water load.[8],[12] There is a high incidence of acute respiratory distress syndrome in the patient with leptospirosis.[11],[13],[14] Dopamine at a renal dose by increasing renal blood flow increased the response to water load in the patient with leptospirosis.[12] Furosemide through its inhibition of Na-K-2Cl cotransport in the thick ascending limb of Henle loop decreased tubular work load and induced diuresis, both of which is advantageous.[15] Its combination with dopamine in the management of acute renal failure is logical. Both dopamine and furosemide decrease energy expenditure of the kidney through vasodilatation and decreased Na transport. In leptospirosis, Na-K-2Cl cotransport in the pulmonary alveolar epithelial cell at the basal border is increased.[16] This favors Na entry into the alveolar epithelial cell and the alveolar space. Patients with leptospirosis are thus prone to develop pulmonary complication. Furosemide through the inhibition of Na-K-2Cl cotransport offers another advantageous effect besides diuresis. Na influx in the alveolar epithelial cells is decreased, and Na entry into the alveolar space is reduced. Pulmonary edema can be prevented.

The result of this study agrees with the authors' previous result in malarial renal failure but conflicts with the experience of others of the failure of dopamine and furosemide in improving the renal function.[2–4] Acute renal failure seen in the hospital, especially in the intensive care unit, is usually due to multiple causes. The problem is often complicated. Several factors including underlying diseases, hemodynamic alterations, nephrotoxicity, and immune mechanism are likely to be involved, which could explain the failure of dopamine and furosemide. In this study as well as the previous study on malaria, there is only a single infectious cause without complications.[1] It is clean acute renal failure where only hemodynamic changes play the role. Like in malaria, this regime of treatment does not benefit leptospirosis patients with severe renal failure.

In conclusion, this study shows the beneficial effects of the combination of dopamine and furosemide in mild acute renal failure in leptospirosis with the serum creatinine ranging from 2 to 5 mg/dL and FE_Na between 1–2%. It is felt that this combination could be useful in the management of mild acute ischemic renal failure due to a single insult.