A-List Kidney Problem

Blood in the urine (hematuria) occurs in 10% of children on occasion. It may be microscopic, detected only with a dipstick or high magnification. It may be gross, with urine that looks like cola, red wine, or cherry Kool Aid. Sometimes kids have microscopic hematuria with intermittent episodes of gross blood. These children often have IgA nephropathy (IgAN).

Many patients with IgAN suffer no symptoms and diagnosis requires kidney biopsy, so the exact incidence remains unknown. In the US, about 0.5 new cases per 100,000 children occur annually. In Japan, the incidence is 10-fold higher. No one knows the cause of IgAN, but we assume that the immune system lies at fault.

Glomerular Tuft: C=Capillary
Glomerular Tuft: C=Capillary

The diagnosis currently relies on the presence of IgA deposits in the glomeruli, the filtering units of the kidneys. A portion of a glomerulus (a tuft) is shown in the diagram. Blood flows through and gets filtered in the capillaries (red C’s). Epithelial cells surround the capillaries (orange arrow), while mesangial cells (blue arrow) fill the “stalk” region of the tuft.

Using special techniques we can see IgA in the mesangial region of the glomerulus in this disorder. There may also be extra cells in that area, known as mesangial proliferation.

The course of IgAN varies from limited progression (or even some episodes of spontaneous remission) to rapidly progressive kidney failure. Kidney function measurements guide management:

  • Estimated glomerular filtration rate (eGFR)
  • Blood pressure (BP)
  • Protein:Creatinine ratio (P:C)

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Nephrologists reserve biopsy, an invasive procedure, for children with abnormalities of at least one of these measures of kidney function, or children with multiple episodes of gross hematuria. Usually patients need no treatment if all measures of kidney function are normal, other than annual observation.

Elevated BP requires treatment, usually with anti-angiotensin therapy (ACEIs or ARBs, in doctor-speak). These agents benefit the kidney beyond their ability to lower BP, especially with elevated P:C ratio. If the P:C is more than 1 mg/mg, then anti-angiotensin drugs should be given even if the BP is normal! After 6 months of therapy, if the P:C remains more than 1, then a 6-month course of steroids should be discussed. Fish oil may also be considered with persistent protein in the urine.

When the eGFR falls rapidly, often associated with crescents (a type of glomerular scar where epithelial cells multiply) on the biopsy, aggressive therapy with steroids and strong immunosuppressants (cyclophosphamide or azathioprine) may reverse the disorder. A number of other drugs can be used in IgAN, but none have proven benefit at this time.

The prognosis of IgAN depends on P:C, BP, and findings on the biopsy at diagnosis. If no high-risk abnormalities are present for these 3 factors, the 20-year survival without dialysis for both children and adults was 96%. If P:C>1, BP>95th percentile, and unfavorable biopsy findings were present, only 36% of patients maintained kidney function for 20 years.

Want more information?
N Engl J Med 2013:368:2402-14.  DOI:  10.1056/NEJMra1206793



When Good Kidneys Go Bad

Perhaps the diagnosis surprised the family. A previously healthy child became more and more fatigued, ultimately resulting in a trip to the doctor and some blood tests. Perhaps it was the long-anticipated-but-dreaded progression of a known condition. Either way, a child’s kidneys have reached the point of  no return. What now?

What level of kidney function requires treatment?

Current dialysis achieves 10-15% of normal kidney function. In the case of a patient with a progressing kidney disorder, planning for replacement of kidney function should begin when estimated glomerular filtration rate reaches 20-30% of normal.

What is dialysis?

Dialysis treatment removes excess fluid and chemicals from the blood by filtering it. The trick is removing enough of things like sodium, potassium, magnesium, phosphorus, and acid without removing too much. Two methods of dialysis exist at this time, hemodialysis and peritoneal dialysis.

Click to enlarge
Click to enlarge


In this form of dialysis, the patient’s blood is taken out of their body, run through an artificial kidney machine, and then returned. Typical treatments take 3 to 4 hours and are performed in a dialysis center 3 days each week. Blood can be accessed using a large intravenous tube in the neck veins or, in adults and larger children, a fistula. A surgeon creates a fistula by connecting an artery to a vein, usually in a forearm. After several weeks, the connecting vessel becomes enlarged. Needles can be inserted and used with the same level of blood flow as the plastic tube. Fistula’s provide better dialysis and have fewer risks of infection than the large intravenous tube.

Some dialysis centers now offer home hemodialysis. Patients’ and their families must learn to stick a fistula and perform the treatments themselves. There are many advantages to this situation, although many centers will not accept children for this treatment option.

Peritoneal dialysis

Peritoneal dialysis involves placement of a plastic tube into the tummy of the patient, the peritoneal space around the bowls. Lots of tiny blood vessels flow through this membrane. By putting fluid in and out of the peritoneal space, fluid and chemicals can be removed from the patient. In children we often use a cycler to do this job. This small machine sits by the patient’s bed and runs fluid in and out while the child sleeps. In another form of peritoneal dialysis, the fluid is changed 4 to 6 times each day over 24 hours.

This type of dialysis is performed by the patient and family at home, so it interferes less with school or work. Monthly lab monitoring and doctor visits are necessary.

What is transplantation?

Ultimately, the goal of nephrologists is to transplant every patient with permanent kidney failure, especially children. A new kidney can be obtained from a healthy relative or other volunteer, or it may be donated by a deceased person. Surgeons can attach the new kidney into the patient, most often in one of the groins. The non-functioning “native” kidneys can almost always remain in place.

Kidney transplant can provide a very normal quality of life, but it is not a complete cure. Patients must take medications to prevent rejection as long as they have the kidney.
These medications can make the patient more susceptible to infections and cancers since they tone down the immune system. Patients with transplants require life-long monitoring of kidney function, medication levels, and other potential side-effects. Despite this list of problems, transplantation is the best therapy for kidney failure and should be the goal for most patients.

A new information sheet about dialysis and transplantation is available on the Information Page of this web site.

Nutcracker Hell

My Daughter as a Nutcracker Mouse
My Daughter as a Nutcracker Mouse

The first week of December, for much of my adult life, brought incredible stress. Not from holiday shopping or social demands; this 10-day period was christened Nutcracker Hell Week.

My daughter Danced (the capital D is intentional) and dance companies live and die by revenue from The Nutcracker. Friday, Saturday, and Sunday after Thanksgiving were filled with dress and technical rehearsals. The following week included shortened versions of the ballet for school groups during the day, with performances Thursday evening through Sunday afternoon. Until she got licensed, I had to drive her to all this stuff, often waiting in the wings during director’s notes. By the end of the week, I started twitching if I heard Tchaikovsky’s notes reproduced on the grocery store Muzak.

The Nutcracker Syndrome produces a different kind of hell. This disorder produces left kidney pain, beginning in the flank and often moving toward the groin. The problem usually occurs with obviously bloody urine, but can be accompanied by only microscopic blood in the urine, or even no blood. When physicians see these patients, they think it must be a kidney stone, but there is no stone.

So what causes such excruciating pain?

Click to Enlarge
Click to Enlarge

Two large blood vessels lie on either side of our spines. On the left side of the spine is the aorta, the major artery bringing blood from the heart to the body. On the right side is the vena cava, the vein that returns blood to the heart. The left kidney sits just to the left of the aorta. When blood leaves the kidney, it must get to the vena cava by going across the aorta. Normal anatomy (figure at right) has the kidney vein crossing in front of the aorta and under a vessel that feeds blood to the gut, the superior mesenteric artery. In some people, the left kidney vein can get compressed between the aorta and this mesenteric artery. Pressure can build up in the kidney (renal) vein, producing pain and bloody urine when tiny vessels in the kidney swell and rupture. In this anatomic situation, the nutcracker syndrome can often be diagnosed by comparing the ratio of the blood flow in and diameter of the renal vein as it crosses under the mesenteric artery to when it leaves the kidney. If the ratio is 4 or more, then the syndrome is highly likely. Magnetic resonance arteriography may be needed to confirm the diagnosis.

Click to Enlarge
Click to Enlarge

Other anatomic variations make the syndrome more likely than the normal picture above. Sometimes the renal vein runs behind the aorta. This large muscular artery can intermittently compress the smaller, softer vein against the spine. In other cases, the renal vein may be split into two vessels. One may flow in front of the aorta and the other behind.

So how do we treat this condition? In adults, a number of invasive interventions have been used successfully. Stenting of the renal vein, surgical bypass of the blocked area, and moving the kidney down to the groin (autotransplantation) have all been used successfully. In children, the condition often resolves spontaneously with growth, particularly an increase in the body mass index as these kids go through puberty. Increases in the perivascular fat pads may increase the angles between these arteries, preventing such severe compression. Surgical correction is generally reserved for severe cases that do not appear to be resolving over a period of months.

The Nutcracker can seem like hell, but the nutcracker syndrome can be a literal hell while it lasts. This rare cause of kidney pain and bloody urine must be kept in mind in the differential of kidney stones, especially when the rock cannot be found.





A Rough Road Ahead

Last month, a baby came into the world without kidneys. This is not generally a topic for news coverage (it happens more often than you think), but this girl’s mother is U.S. Rep. Jaime Herrera Beutler. Despite prenatal warnings about the grave prognosis, the Representative chose to continue her pregnancy with periodic intrauterine saline infusions. The fluid substitutes for fetal urine in utero, allowing better lung development and preventing the deformities induced by uterine compression in the absence of amniotic fluid.* This procedure has been used since the 1990s with variable success.

Abigail, the infant, was born prematurely, at 28 weeks of gestation and a weight of 2 lb 2 oz. A baby this premature has a hard road ahead of her, even if everything else is normal. Having no kidneys just makes things that more complicated.

Two studies examined single-center prognosis for infants on chronic dialysis, generally peritoneal dialysis (treatment the Beutler child is undergoing). One from Miami examined all chronic dialysis patients who started treatment in the first year of life. Of 52 patients, 20 (38%) died in the first year of life, mostly within the first month of life. Over up to 25 years of observation, the mortality totaled 54%. They did not report the gestational age of their patients, and no child was reported to be completely anephric.

The other study came from the University of Minnesota. It examined only infants started on peritoneal dialysis before 28 days of age (23 babies). Gestational age in this series ranged from 31-40 weeks (average 37 weeks) with 39% considered premature (<17 weeks of gestation). Survival at 1 year was 52%, with half of the deaths occurring before the infant could be discharged to home. Once again, no infant with complete absence of kidneys was reported.

Both studies confirm that getting these kids to an appropriate size for transplant (~10 kg body weight, generally at 15-18 months of age) can be a battle. Most children suffered infections and other problems leading to hospitalizations during that period. The Minnesota groups averaged 6 admissions each in the first year of life after neonatal discharge (average discharge occurred after 3 months of hospitalization, so those 6 re-admissions occurred within a 9-month period).

These infants also require support beyond dialysis and medications. Forced feedings via a tube were required in 94% of babies discharged on home dialysis in the Minnesota series.

The good news is that once these children get to transplant, they generally do as well as other children with end-stage kidney failure. Patient survival remains stable after 2 years of age, and the 5-year transplant graft survival rate is 83%, similar to that of older children transplanted in the same era.

Both of the studies discussed here started with infants on dialysis; we do not know how many parents chose not to pursue aggressive treatment for their critically ill offspring

Peritoneal dialysis allows us to save about half of the infants whose kidneys fail in the first months of life. However, these children often have multiple admissions over that first year of life, and they will be technology-dependent for their entire lives. All of these factors need to be weighed by the parents before embarking on infant dialysis. .

*Use of this illustration for 1 year online would cost me $282; click over to the Netter Illustration and view it with the watermark. You will get the general idea.

Uncommon Rocks

Kidney stones seem to be as common as rocks. A variety of factors can contribute to their formation, but sometimes an interesting cause can be identified. Protein in the urine can be a tip-off that something unusual is happening.

Dent’s Disease

This X-linked recessive disorder causes problems in the function of the kidneys’ proximal tubules, leading to:

  • Hypercalciuria (high urine calcium)
  • Nephrocalcinosis (calcium deposits in the kidney tissue)
  • Kidney stones (calcium crystals in the collecting system of the urinary tact)
  • Proteinuria (urine protein)
  • Rickets (poor bone mineralization)
  • Chronic kidney disease with loss of function

Because the disorder links to the X-chromosome, most affected patients are male. Girls may show mild signs and symptoms, but chronic kidney disease is rare.

In 60% of cases, a gene called CLC-5 shows a mutation. Abnormalities of OCRL1 cause another 15% of cases. The genetic cause is unknown in about one-quarter of patients who otherwise fit the diagnosis.

Click to Enlarge
Nephron: Click to Enlarge

Proximal Tubule Function

The kidneys receive about 20% of each heartbeat’s blood for filtration and removal of wastes. Most of this blood flows through special clumps of blood vessels that allow watery material from the blood to pass into Bowman’s Space, the first portion of the nephron. From there this filtrate enters the proximal tubule, the workhorse of the kidney. This part of the kidney retains most of the fluid and chemicals filtered into the nephron.

When I want to clean up the mess in a room, I pick up the trash and dispose of it. The kidney takes a different approach, instead sweeping everything in the room into the trash and then removing what it wishes to keep. The proximal tubule retains 2/3 to 3/4 of this good stuff for the kidney.

Severe proximal tubule dysfunction results in Fanconi Syndrome. The kidney wastes everything that it should retain, including bicarbonate, potassium, phosphate, protein, glucose, and calcium. In Dent’s disease the dysfunction is less severe. While excess urine calcium and protein is necessary for the diagnosis, phosphaturia and glucosuria are variable. Dent’s disease is ruled-out by the presence of renal tubular acidosis due to bicarbonate losses.


Affected boys often develop chronic progressive kidney disease, with 30-80% developing permanent kidney failure over time. Girls are generally asymptomatic carriers; if they have signs or symptoms, they are usually mild and cause no long-term kidney damage.

Treatment currently focuses on reducing stone risk through treatment of hypercalciuria with sodium restriction and thiazide diuretics. Other general treatments for chronic kidney disease should also be employed as necessary.



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