Dietary Treatment of the

Kidney Function Restoration Program

Foods not to eat when you have Kidney Disease

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The nephrotic syndrome has been mentioned throughout the book as something that is different from kidney failure, but which often ends up causing kidney failure. Let's examine exactly what the nephrotic syndrome is and how it can be treated.

The nephrotic syndrome is defined as a very high rate of excretion of protein in the urine (greater than 3.5 g per day), a low level of albumin in the blood (less than 3.5 g per dl), and edema (swelling of soft tissues, such as the ankles, the abdomen, and around the eyes). Most patients with the nephrotic syndrome also show markedly elevated levels of cholesterol and other lipids. This condition is a form of kidney disease distinct from kidney failure. The causes are numerous, including toxic reactions to drugs, allergic reactions to bee stings, various infections, cancer, a huge list of systemic diseases, and various disorders of the heart and blood vessels. For unknown reasons, young children are often affected. Cow's milk protein intolerance is said to cause the nephrotic syndrome. It is hoped that further studies will be done on the effect on the kidney of possible allergy-inducing proteins in food. Sometimes the nephrotic syndrome disappears entirely after a few months. However, patients with the nephrotic syndrome often develop renal failure and progress to dialysis.

In the past, the low albumin concentration in the serum and the pronounced loss of protein in the urine of patients with the nephrotic syndrome led nephrologists to advise a high dietary protein intake. In the mid-1980s, however, several reports appeared documenting that dietary protein restriction not only reduced urinary loss of protein, but in some cases led to an increase in serum albumin level. As yet, no explanation for this paradoxical effect has been proposed. (Note: In these studies, most doctors used a low-protein diet instead of the supplemented very-low-protein diet that has been suggested in this book.)

Having observed serum albumin levels rise in some patients without the nephrotic syndrome when given a supplemented very-low-protein diet, my colleagues and I decided to try this regimen in patients with the nephrotic syndrome due to any cause. To our surprise we found that protein excretion decreased in all patients and serum albumin rose in most. Nevertheless, 12 of these patients who presented with glomerular filtration rates of less than 30 ml per min (about one-quarter of the normal value) eventually progressed to dialysis. The remaining 5 patients, who presented with GFRs greater than 30 ml per min, showed surprising improvement: Albumin rose to normal, cholesterol fell almost to normal, and protein excretion in the urine decreased markedly over the ensuing months. In other words, the nephrotic syndrome of these patients virtually disappeared. These changes were not the result of falling GFRs; in fact, GFRs rose in 4 of the 5 patients. Later, 4 of these 5 patients resumed a normal diet.

Subsequently, Simin Sistani and I have found that one type of nephro-tic syndrome in particular benefits from this approach, a disease known as focal segmental glomerulosclerosis, which was particularly hard to treat in the past. In patients with the nephrotic syndrome, in general, the greater the amount of protein lost in the urine before starting the diet, the greater the response to diet. In fact, patients who had low amounts of protein in their urine showed no benefit from the diet, while patients with severe nephrotic syndrome usually showed a marked fall in urinary protein; only one relapsed. This finding is the opposite of conventional wisdom, which holds that patients with pronounced urinary protein are poor candidates for protein-restricted diets.

Here are some examples of people with the nephrotic syndrome who have responded to dietary treatment.

Arnold Sanderson is a retired research analyst for the Health Care Financing Administration. He was referred to Johns Hopkins one year ago with a history of hypertension for 40 years and high urinary protein for 9 years. A kidney biopsy had shown a type of glomerular disease often associated with the nephrotic syndrome called membranoprolif-erative glomerulonephritis. Despite a protein-restricted diet (40 g per day) and an ACE inhibitor, his serum creatinine level and the amount of protein in his urine had progressively increased. Nevertheless, he had always maintained normal levels of serum albumin and cholesterol. He had no symptoms at all, and his physical showed nothing out of order. Initially, the following results were obtained from the laboratory: serum creatinine 3.8 mg per dl, serum albumin 4.0 g per dl, GFR 26.3 ml per min, urine protein 4.8 g per day. He was placed on a very-low-protein diet supplemented by essential amino acids and has been checked every two months. Three years later, the lab data showed only moderate worsening: serum creatinine 4.7 mg per dl, serum albumin 3.8 g per dl, GFR 18.3 ml per min, urine protein 1 g per day. He remains free of symptoms. Perhaps in response to this diet, Arnold's nephrotic syndrome has stopped progressing although his kidney function has declined. His compliance with the diet has been excellent.

—Dialysis deferral: 3 years

Lavinia Leonardo is a 50-year-old resource manager for the army. She was referred to us for treatment in 1995. She had been diabetic since her second pregnancy 28 years ago. Oral antidiabetic drugs had treated the condition well until four months ago, when she needed to start on insulin injections. Ten days later she developed generalized swelling and was found to have a serum albumin level of 1.3 g per dl and urinary protein of 20 g per day. A kidney biopsy showed focal segmental glomeru-losclerosis and mild diabetic glomerulosclerosis. She had been intermittently hypertensive for years and was taking an ACE inhibitor as well as other antihypertensive drugs and diuretics. She complained of fatigue, muscle cramps, swelling, and aches across the shoulders. Physical exam showed only ankle edema. Laboratory data were as follows: serum albumin 2.5 g per dl, serum cholesterol 415 mg per dl, serum creatinine 1.2 mg per dl, serum urea nitrogen 39 mg per dl*, GFR 29.8 ml per min.

Lavinia was placed on a very-low-protein diet supplemented by a double dose of essential amino acids (20 g per day). Over the next few months, her kidney disease disappeared: Her serum albumin concentration rose to normal, urine protein disappeared, and GFR rose to normal. The diet and the supplement were discontinued, and she exhibited no signs of kidney disease for the next four years.

Then, early in 2001, she developed marked protein excretion again (19 g per day) and an even more severe drop in serum albumin level (to 1.8 g per dl). Serum cholesterol rose to 340 mg per dl. Unless she consumed salt, she noted little swelling. (She was still taking diuretics plus a statin and limiting salt intake.) Resumption of the low-protein diet plus supplemental essential amino acids had little effect at first, except that serum albumin level rose slowly. By fall 2001, however, urinary protein suddenly disappeared and serum albumin level became normal. She now has no symptoms at all.

—Dialysis deferral: Permanent

Martha Blomberg is a 44-year-old office worker with the nephrotic syndrome caused by a form of glomerular disease called focal segmental glomerulosclerosis. She was first seen at Johns Hopkins in 1992. She had a very low serum albumin concentration (2.3 g per dl), pronounced urinary protein excretion (11 g per day), and high serum levels of cholesterol (340 mg per dl), LDL cholesterol (242 mg per dl), and triglycerides (294 mg per dl). These lipid abnormalities had persisted despite her taking a statin drug, pravastatin, to counteract them. Her GFR was

*Urea concentrations traditionally have been reported as urea nitrogen concentrations, for historical reasons; urea contains 47 percent of nitrogen by weight.

moderately reduced, 36 ml per min. When placed on a very-low-protein diet supplemented by essential amino acids, she responded slowly but profoundly: urine protein decreased over the next year to about 3 g per day, serum albumin rose to normal (3.7 g per dl), and GFR scarcely changed. By the end of 1994, the diet could be discontinued. Since then she has continued to exhibit urinary protein excretion lower than on admission (about 3 g per day), unchanging GFR, and normal serum albumin concentration. However, high blood cholesterol has continued to be a problem. During 1993 and 1994, her serum cholesterol concentration fell slowly, though not quite to normal levels, presumably as a result of the diet. But early in 1995, her liver function tests (ALT and AST) suddenly became very abnormal. Pravastatin was discontinued, and these tests returned to normal (except for a couple of unexplained lesser elevations in 1997). Serum cholesterol remained high. Tests for hepatitis were carried out and proved negative. Eventually, after much discussion and an attempt at a low-fat diet that proved ineffective, a different statin drug, atorvastatin, was started. For the first time her cholesterol levels are normal, despite continued urinary protein loss (about 1.5 g per day). We will continue to check her for liver damage from this different statin drug. Meanwhile, dialysis has been avoided, apparently permanently. Kidney function is constant after six years, and she has no symptoms on a normal diet.

—Dialysis deferral: 12 years so far

As you can see from these stories, when careful attention is paid to other health problems, a supplemented very-low-protein diet can be extremely effective in helping patients with the nephrotic syndrome avoid dialysis. Similar results were reported in preliminary form from Japan.

The means by which protein restriction improves the nephrotic syndrome are unknown. It seems curious that dietary protein restriction does not reduce protein loss in the urine in patients who lose only moderate amounts. This is the exact opposite of conventional wisdom; it is generally held that protein restriction should not be employed if there is a lot of protein in the urine.

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