Free to Pee etc.

An Illinois Public Radio story caught my eye on Twitter this week. It dealt with a major player in Chicago charter schools and their disciplinary policies. Limitations on bathroom usage meant many young women were bleeding through the mandatory khaki pants during their periods, a less than ideal situation for all involved:

“We have (bathroom) escorts, and they rarely come so we end up walking out (of class) and that gets us in trouble,” she texted. “But who wants to walk around knowing there’s blood on them? It can still stain the seats. They just need to be more understanding.”

They go on to defend the policy, noting that girls who bleed through their pants can tie a sweater around their waist to cover up the damage. Of course, since this is not a usually acceptable part of the dress code, they then announce the names of the girls who are allowed to wear this aberration.

Yeah, please announce to the world the name of the menstruating students. Nothing about that will make them feel self-conscious or awkward.

I haven’t worried about bleeding through for a while now, but I do worry about bathroom access in schools. As a pediatric nephrologist, I take care of a lot of children who would benefit from easier access to the restroom.

  • First up are those children with frequent urinary tract infections (UTIs). One of our defenses against UTI is completely emptying our bladders on a regular basis. This action flushes out any bacteria that have made their way into the interior space. In addition to that, holding urine can cause the bladder to lose efficient function. Children may not be able to empty completely, meaning bacteria are more likely to get a foothold in the bladder and cause trouble. 
  • Second, we must consider children with constipation. A large wad of poop can put pressure on the bladder, its outlet, and its nerves, preventing proper sensation and function. These children must be cleaned out with aggressive stool softening. How inconvenient if the bathroom escort is not available when the poop is ready to pop! Holding it in not only makes constipation worse but further worsens bladder function and makes UTI likely. Adequate fluid intake can also prevent constipation. 
  • Third, a lot of children get kidney stones. Some of these kids have biochemical problems that can be treated, but even those stone-formers could likely prevent such things if they drank enough water. For adults, we recommend enough water to produce 2 liters (66 oz) of urine daily. This means drinking 2-2.5 liters of fluid. At least part of this should be consumed during the school day, necessitating bathroom use. Kidney stones produce debilitating pain, and in the long-run can lead to permanent kidney damage. 

Other considerations include keeping bathrooms clean and functional and safe.

I would like to declare that all people, even students, have the right to use the bathroom when necessary. Not only is holding pee and poop in harmful, but I cannot imagine being able to learn when I’m worried about losing control or bleeding through my clothing.

Join me in showing support for the right to hygienic elimination! You can buy a “Let Kids Pee” ceramic cup or stainless steel travel mug on Amazon (my design is featured above in this post). You will help support this website and the battle we pediatric nephrologists fight on this front.


Sickling Hemoglobinopathy and the Kidney #ExpBio

HbSS from Wikipedia

This year a number of abstracts about sickle cell and the kidney caught my attention, having just initiated dialysis on a patient with HbSS. Since the science forces of the universe seemed determined to focus my attention on this disorder, I gave into their wishes.

Hemoglobin (hb), the molecule that carries oxygen to tissues in our body, is composed of two alpha protein chains and two beta chains. In the HbS mutation, a single change in the beta chain changes the structure of the protein so that when oxygen levels drop, it becomes straighter instead of round, stretching red blood cells into a crescent or sickle shape. Abnormally shaped red blood cells are prone to damage (hemolysis) and may clog the smallest vessels in the body, resulting in organ damage and pain.

Actual Sickle

If a child gets one copy of the HbS gene, then they are a carrier; this condition is also called sickle cell trait and occurs in 1 in 13 African American babies. Most people with trait have no symptoms, although under conditions of low oxygen their disorder may be unmasked. For example, the central part of the kidney (the medulla) has much lower oxygen tension normally. Cells often sickle there and cause damage, so individuals with otherwise asymptomatic sickle trait may not be able to fully concentrate their urine.

If a child gets a copy of HbS from both parents, then they have HbSS, the full-blown sickle cell anemia disease. This happens to about 1 in 365 African American children. These individuals have anemia because the sickling cells don’t last as long as those with normal Hb (3 weeks vs 3 months). The abnormally shaped cells may also impair blood flow to organs cause acute pain episodes, what most people think about with sickle cell disease. In addition, other organs may be damaged by these events, including the brain, heart, lungs, and kidneys.

For more general information about sickle cell disease, including other associated hemoglobin disorders, the NIH has an excellent resource here.

Kasztan M, Fox BM, Speed JS, Townes TM, and Pollock DM:  KIM-1 as a new biomarker for glomerular hyperfiltration and chronic kidney disease in humanized sickle cell disease mice

Your ads will be inserted here by

Easy Plugin for AdSense.

Please go to the plugin admin page to
Paste your ad code OR
Suppress this ad slot.

The first poster on my list dealt with KIM-1 (Kidney Injury Molecule 1) as a new biomarker for kidney damage in a humanized mouse model.They followed glomerular filtration rate (GFR) and urinary biomarkers in HbSS mice and genetic controls every 4 weeks for 24 weeks starting at 8 weeks of age. At that starting point, no differences in GFR or proteinuria were demonstrated. By 12 weeks, the HbSS mice had a significant rise in GFR and proteinuria. By 32 weeks of age, GFR was lower in HbSS than Hb AA mice, even as proteinuria climbed higher. Urine biomarkers demonstrated early KIM-1 as a potential predictor of loss of GFR later in the course. Not included in the abstract was a cohort of patients with HbSS, some of whom have developed elevated KIM-1 excretion. This has the potential to drive important translational studies in the future.

Taylor CM, Kasztan M, Yoder B, Pollock JS, and Pollock D:  Reduced Renal Primary Cilia Expression in Humanized Sickle Cell Mice

The next poster looked at renal cilia in this same mouse model. Ciliary disorders often result in cysts in the kidneys, and patients with HbSS have an increased risk of cyst formation. Kidneys from HbSS mice have reduced ciliary proteins in their kidneys, suggesting reduced numbers or size of cilia in this model. Additional studies applied hypoxic stress to the mice, a maneuver that increased expression of the proteins under study. These experiments are still preliminary, but I would never have guessed that cilia would be a problem in sickle cell kidneys.

Eshback ML, Kaur A, Rbaibi Y, Agarwal Y, Zhang Q, Nolin TD, Tejero J, and Weisz OA:  Hemoglobin Inhibits Uptake of Filtered Proteins by Proximal Tubule Cells: Implications for Sickle Cell Disease and Vitamin D Status

The final poster examined the role of Hb uptake in tubular cells in nickels cell disease. Much of this study occurred in vitro, examining what happened to tubular transport when free Hb gets filtered and the tubules reabsorb it. It competes for transport with a number of other proteins, such as albumin and the vitamin D binding protein. Patients with HbSS have reduced red blood cell lifespan and episodic hemolysis, so they do filter higher amounts of free Hb. They also seem to be much harder to make replete with Vitamin D. These basic science observations may help explain some interesting clinical observations, even though these phenomena would seem unrelated at first glance.

Sometimes an abstract just grabs me; this time, three of them jumped me and made me write about them. All were really good science with excellent presenters, and a lot more information than I’ve included here (click the links, people). Best of luck helping us understand this difficult consequence of a fairly common disorder.

Cool Imaging #ExpBio

Each kidney contains a bunch of discrete units or nephrons that include a filtering unit, the glomerulus, and a tubule that reclaims all the useful stuff from the filtrate. When we discuss how the kidneys work, we often treat the kidney like it’s a single nephron, but it’s a whole bunch of units that need to be on the same page regarding the body’s requirements.

Prior studies have demonstrated that nephrons can signal each other over short distances, but these have been hampered by the inability to look at more than a handful of nephrons at once. Enter a possible solution for imaging of circulation:

Postnov D, Marsh DJ, Holstein-Rathlou N-H, Cupples W, and Sosnovtseva O:  High-resolution optical imaging of synchronization in the renal circulation.

I have a difficult time doing this poster justice, since I do not have images to post. Suffice it to say that they have a laser speckle imaging set up that provides spatial resolution to 0.8 μm per pixel. They were able to analyze clustering of flow in ~1.5 x 1.5 mm^2 areas of renal cortex and gauge how well synchronized flow was.

This is a cool toy I would love to play with, and I can imagine some interesting studies coming from this new technology. If you missed the poster, check out the abstract above.

SGLT2 in the Diabetic Kidney #ExpBio

Empagliflozin (original image )

Glucose in the glomerular filtrate gets reabsorbed in the proximal tubule by two transporters, known as sodium-glucose cotransporters (SGLT). The bulk of the glucose gets removed by SGLT2 with a smaller amount retrieved farther down the tubule by SGLT1. With normal blood sugar levels, these molecules can reclaim all the filtered load of glucose, leaving none of this sugar in the urine.

In diabetes, glycosuria occurs when blood sugars exceed the limits of SGLTs. Agents have been around for a while that inhibit these transporters, but only recently have inhibitors of SGLT2 been shown to reduce blood glucose in diabetes in clinical settings. Large trials over the past couple of years have shown additional benefits of this class of drug beyond their ability to reduce hyperglycemia. They seem to reduce cardiovascular events and to have beneficial effects on progression of diabetic kidney disease.

Liu Z, Hall E, and Singh P:  SGLT2 inhibition decreases oxygen consumption and increases oxygen tension in diabetic rats

Liu et al present a possible mechanism for these beneficial effects at this meeting. They made rats diabetic with streptozocin (a model of type 1 diabetes, not the condition these drugs are used for clinically) and examined oxygen consumption and tension in their kidneys.

Sodium reabsorption drives metabolic demand for oxygen consumption in the kidney. In addition to allowing glucose to escape, SGLT inhibitors prevent sodium reclamation and reduce this demand. They found that diabetes increased renal oxygen consumption as previously demonstrated and the SGLT inhibitor Empagliflozin (EMPA in figure) prevented this change. Oxygen tension in the renal cortex was reduced by diabetes, with SGLT inhibition once again preventing this change. Medullary oxygen tension was not affected by these states.

Click link to abstract to see other specific data

SGLT inhibitors may have important effects in organs aside from lowering blood glucose. Studies like these may help us understand these interesting new agents, and point toward other therapeutic targets.

Earnest Starling Lecture 2018 #ExpBio

On Sunday David Mattson presented the Starling Distinguished Lecture of the American Physiological Society Water and Electrolyte Homeostasis Section. His talk addressed the role of inflammation in salt-sensitive hypertension, using the Dahl salt-sensitive rat and some supporting human data.

About half of human adults have hypertension, and about half of those patients are salt-sensitive like this rat. Feeding this rodent a high salt diet leads to rising blood pressure and albuminuria, with enlarged glomeruli, tubular damage, and inflammation. Other types of rats given the same level of sodium intake do not develop these findings. Studies from people with hypertension also show increased lymphocytes in their kidneys, suggesting that there are parallels with human disease.

In a series of experiments, Dr. Mattson showed that there were increased B and T cells in these rat kidneys and that the immune cells were activated and producing a number of cytokines. Inhibiting the presence and activity of these immune cells attenuated both the hypertensive and renal damages induced by salt loading. They then took genes identified in human association studies of hypertension and mutated the analogous genes in rats. They transplanted bone marrow from these mutant animals into Dahl rats without the mutation, so only hematopoietic cells carried the mutation in question. When salt loaded, these rats showed less hypertension than intact Dahl rats, suggesting that the immune response provided major input for hypertension.

What about the role of hypertension beating up on these kidneys? Dahl rats have poor autoregulation, so systemic hypertension gets transmitted to the kidneys. They placed an aortic cuff just above the left renal artery in rats and used it to maintain a normal blood pressure into that kidney. The right kidney saw and felt the higher pressure. This maneuver alleviated the inflammatory response in the cuffed kidney.

In the Dahl model of salt-sensitive hypertension, both inflammation and barotrauma appear to contribute to kidney damage. The story does not end here; the Mattson lab is presenting more fascinating work on this topic at this year’s meeting.

Smells and Tastes #ExpBio

This year the Renal Section Young Investigator Award goes to a favorite of mine, and not just because her work has let me create a great image of the kidney. Jennifer Pluznick, now an Associate Professor at Johns Hopkins, began her journey in physiology as a doctoral student at University of Nebraska while I was there. While a post-doctoral fellow at Yale, she began exploring G-protein-coupled-receptors (GCPRs) in the kidney, especially those previously involved with smell, and her lab now explores their role in kidney function. Her lab logo is pretty cool; I’ll wait while you take a look.


Olfactory receptors constitute the largest gene family with 350 members in humans and approximately 1000 members in rodents. So far, 18 of these olfactory receptors have been located in the kidney with an additional 11 taste-associated GCPRs and 76 without known ligands. She first studied olfactory receptor 78 (Olfr78), an interesting chemosensor that localizes to the afferent arteriole, a major site of control for blood pressure and kidney function. It’s ligands (activators) include short-chain fatty acids such as acetate and proprionate, molecules derived primarily from our gut microbiota. Proprionate has been shown to cause the release of renin via its interactions with Olfr78.

Changes in gut microbiota have been associated with changes in blood pressure, so her lab wanted to explore changes in the metabolites that might occur with hypertension. They implanted micro pumps into conventional mice and into germ-free mice (mice in a plastic bubble) and infused them with angiotensin II, an established model of hypertension. Germ-free mice showed no changes (no microbiome, no metabolites), but of more than 800 substances studied, 13 were unregulated with angiotensin II infusion. Some are uremic toxins and many are known to lower blood pressure; perhaps our microbiome is trying to help us out when our kidneys fail or our blood pressures otherwise get elevated. After all, our death would not be particularly helpful for the bacteria residing in our gut. Also interesting were some sex-specific changes identified. The meaning of these differences should provide fertile ground for further study.

As expected, Dr. Pluznick delivered an excellent presentation of her impressive work. If you aren’t here, you missed a great talk. You can still catch her on the TED stage:

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.