We understand kidneys must function on several levels to sustain the body’s internal balance, also known as homeostasis. This is done by regulating water, urine accumulation, pH balance, and electrolyte balance in the body. How does the kidney do this? The kidney has glomerulus inside it that acts as filters to make urine by filtering the blood. The kidney has many glomeruli in each of the kidneys, which does filter of the blood. Other than this, glomeruli shield body protein to get into the urine. Proteinuria, as it may be called as when the filters that shield the protein into the urine fail, it results in proteins like albumin leak into urine. Too much protein can also be a reason for proteinuria.

So, this is where PLN or protein losing nephropathy comes into the picture. We will know what it is, what causes it, what its symptoms are, and many more aspects of PLN in this article.

PLN – Protein Losing Nephropathy – What is it?

PLN or protein losing nephropathy is a glomerulus disease. When this issue arises, the shield to protein is lost, and there is a loss of protein into the accumulated urine. This protein is poisonous to the kidneys. When this issue is persistent and not controlled, protein losing nephropathy can ultimately result in CRD-chronic renal disease. This eventually results in the death of the patient.

Ultimately, people suffering might need human euthanasia due to CRD. In some cases, it may result in death.

PLN – What happens?

PLN – Protein losing nephropathy occurs due to primary three types of glomerulus conditions:

  • Glomerulonephritis
  • Amyloidosis
  • Glomerulopathy

A normally functioning glomerulus is a sieve that permits free filtration of creatine, water, urea, and other smaller molecules from it. However, the sieve does not allow any negatively charged or large molecules through it. Albumin- a protein whose molecular size is large, does not go through a normally operating glomerulus. But a damaged glomerulus can have wider pores as compared to a normal one. A disease impacted glomerulus can also have a disrupted charged surface.

What happens in glomerulonephritis?

The damage to the glomerulus in this condition is because of the complexes of antigen-antibody, which blocks the pores. It clogs the activate complement. Eventually, the condition results in an inflammatory response. Activation of platelets exacerbates the harm done to the glomerular capillary.

What happens in glomerulopathy?

Familial glomerulopathy is a genetic condition. This results in proteinuria. Eventually, the condition can advance to renal failure.

What happens in amyloidosis?

In this condition of amyloidosis, the protein gets accumulated within the glomerulus.

Causes of protein losing nephropathy

The two major diseases result in PLN, and they are:

  • Amyloidosis
  • Glomerulonephritis

Other causes of Proteinuria

  • Swelling
  • Dehydration
  • Low BP
  • Fever
  • Extreme activity
  • Increased stress
  • Kidney stones
  • Extremely low temperatures
  • Daily intake of aspirin

Some severe disorders can also result in PLN like

  • Immune issues like lupus
  • Multiple myeloma
  • Preeclampsia, seen in some pregnant ladies
  • Cardiovascular disease
  • Red blood cells condition – Intravascular hemolysis
  • Kidney cancer
  • Heart issues

Signs and Symptoms of protein losing nephropathy

Protein losing nephropathy is hard to detect in the beginning, as there are no signs associated with it. But as the disease advances, one can notice some symptoms. These signs can be observed due to inappropriate kidney function and other associated internal impacts.

Some of the primary signs and symptoms that can be noticed

  • Frequent urination
  • Bubbly / Foamy pee
  • Shortness of breath
  • Appetite loss
  • Stomach upset
  • Nocturnal muscle cramps
  • Vomiting
  • Anorexia
  • Nausea
  • Edema – A condition where there is fluid accumulation in the body cavities or tissues unusually
  • Polydipsia- A condition of secondary polyuria with excessive drinking
  • Melena
  • Dehydration
  • Polyuria – A condition of increased passing of urine as the kidney loses the capability to concentrate/accumulate urine
  • Tiredness
  • Loss of weight

Among less noticed symptoms

  • Seizures
  • Blindness
  • Oral ulcers
  • Bleeding issues
  • Uremia
  • Rise in BP, resulting in damage to eyes, kidneys, brain, and heart

Risk factors of PLN

A person may be more likely to get PLN if:

  • Obese
  • Over 65 years
  • Kidney illness in the family
  • Native American, African American, Pacific Islander descent or Hispanic
  • Orthostatic proteinuria- Condition where protein leakage is more while lying down or standing

When should you visit a doctor?

When your urine test displays protein presence in your urine, then ask your physician if there is any further testing required. Sometimes, protein presence can be short-lived or temporary in the urine. To confirm the protein presence, a repeated urine test may be suggested by your doctor the next morning or after a couple of days. Post the test results, it can be confirmed if the protein present in your urine is temporary or a sign of Protein Losing Nephropathy.

Other than this, some other associated tests may be done to determine the presence of protein in your urine and if it is of any concern.

For people with diabetes, your physician may consider checking for protein in urine for even smaller amounts. This type of protein presence is also referred to as Microalbuminuria. It is generally carried out once or two times a year. If there are any rising protein amounts or developing proteins present in your urine, this can potentially direct as a preliminary sign of kidney damage due to diabetes.

Diagnosis of PLN

  • Urinalysis
  • Urine culture
  • Blood pressure check
  • Abdominal ultrasound
  • Kidney biopsy

The following other tests are considered for evaluating PLN

  • Chemistry profile
  • Chest X-rays
  • UPC- Creatinine: urine protein ratio
  • CBC-Complete Blood Count
  • Chest X-rays
  • ANA-test for immune disease-lupus Kidney biopsy is useful in some instances to diagnose and stage the disease

The above tests are carried to evaluate and confirm the medical diagnosis of the disease severity. This will assist the necessary treatment and right plan for monitoring.

What changes can be seen in lab work associated with PLN?

The following changes are observed in the various tests carried out in the laboratory:

Urine protein levels are noted in Urinalysis. Other changes include enhanced cholesterol or hypercholesterolemia and lowered albumin or hypoalbuminemia.

Other common changes observed as the disease progresses include:

  • Proteinuria
  • Azotemia – Rise in creatine and BUN-two blood parameters
  • Urinary infection
  • Isosthenuria-dilute urine

How can PLN be treated?

There are several options for treating PLN. The primary objective of PLN treatment is to minimize the loss of protein into the urine from the kidneys. The overall quality of life must be improved. The treatment methods generally involve dietary and lifestyle changes along with required medication.

The treatment is figured out based on the root cause of the problem. No treatment is required if the condition is mild or short-lived. However, in diagnosis, it is essential to figure out the right treatment to PLN before the kidney fails. In the process, medication is prescribed. It is specifically for people with high BP and diabetes or either of the conditions.

For PLN, the following are primarily recommended:

  • Angiotensin-converting enzyme-ACE inhibitors
  • ARB

How can PLN be monitored?

Once PLN is identified, it is essential to keep monitoring the condition of the patient to avoid the unlikely. Lab work and BP monitoring are primary amongst them. Urine culture and Urinalysis may be repeated depending on the severity of the disease. Each patient will need monitoring depending on the condition and their severity. Accordingly, the monitoring steps are suggested to the patient.

Lifestyle and dietary changes to improve the condition of PLN

Your diet plays a major role in preventing the kidney from damage.

The following dietary changes have to be made for better kidney functioning:

  • Since kidney disorder arises from protein loss, you may think that a protein-rich food/diet can aid in restoring the loss. But it is not suggested as extra protein can harm the functioning of nephrons and eventually result in renal damage/insufficiency. Medium to low protein diet is recommended that you can work with a dietician and doctor.
  • A diet with low sodium is suggested as extra sodium results in the retention of salt and fluids in the body. It eventually makes the body swell and in hypertension.
  • Minimizing fat can avoid cardiovascular illnesses that are related to kidney disorders.

Foods to include

  • Lean meats
  • Peanut butter
  • Dried beans
  • Soybeans

Frozen / fresh fruits

  • Apples
  • Pears
  • Bananas
  • Watermelons
  • Oranges

Frozen / fresh veggies

  • Tomatoes
  • Green beans
  • Lettuce
  • Low-sodium veggies canned
  • Rice
  • Potatoes
  • Whole grains
  • No-salt snacks
  • Tofu
  • Cottage cheese
  • Butter
  • Milk

Processed foods, high-sodium meats, canned meats, frozen dinners, salted snacks, pickled veggies, high sodium seasonings, and salted bread are some foods to avoid in this condition of PLN.

Dietary tips 

  • Suggested protein intake is 1 gram/kg each day. However, it may vary with the present condition of your kidneys.
  • 400mg/meal of sodium intake is recommended.
  • Limit salt and its seasonings.
  • Prefer home-cooked meals.
  • Cook food with coconut, olive, or other healthy oils.
  • Limit using salt
  • Select fresh veggies and low-sodium or no-sodium canned veggies.

Complications due to PLN-Protein Losing Nephropathy

The following complications can arise due to Protein Losing Nephropathy:

  • Hypertension
  • Hypercoagulability
  • Hyperresponsiveness of platelets
  • Loss of antithrombin III through urine. It is a natural anticoagulant.
  • Formation of thromboembolus that sticks in the pulmonary vasculature. This results in dyspnea in acute cases.

Drugs employed in the treatment of Protein losing Nephropathy

The drugs employed in treating Protein Losing Nephropathy or PLN is based on the condition that caused PLN and the target to treat it. As stated above, ACE inhibitors and ARBs have been employed earlier to handle the cases of protein losing nephropathy. These were combined with a diet with low protein content to assist the treatment. However, currently, the medicine industry has developed, and other medications are used singly or in combination to handle PLN. The results have been good with better management of PLN.

Let us look at most of the drugs that are used and how do they treat/deal with the condition of Protein Losing Nephropathy:

ACE or Angiotensin-converting enzyme inhibitors

  • These ACE inhibitors do not let angiotensin I to convert to angiotensin II. This way, these medicines aid the kidneys in many ways.
  • They minimize glomerular hydrostatic transcapillary pressure.
  • They enhance the preservation of slit diaphragm and GBM heparin-sulfate.
  • Aldosterone synthesis is reduced.
  • They assist in reducing mesangial injury.

Medicines in this category that are used in 12-24 hours

  • 0.25 mg- 0.5 mg/kg-Benazepril
  • 0.25 mg- 1 mg/kg Enalapril

However, BP and renal functioning should be monitored.

ARB – Angiotensin receptor blockers

  • These medications block angiotensin I selectively. However, it does not impact angiotensin II. This function aids in renal vasodilation and sustenance.
  • Aldosterone synthesis is minimized, and its generation is reduced, resulting in minimized potassium, vasodilation, and enhanced sodium generation.
  • Plasma concentrations are enhanced, but BP lowering is not counteracted.
  • It aids in minimizing proteinuria, ameliorating glomerulus, inflammatory infiltration of cells, and structural tubular change.

Medications used generally in this category in 12-24 hours range

  • 0.25 mg- 2 mg/kg-Losartan
  • 5mg/kg-Irbesartan

Combining ARB and ACE

The blockage is maximized with both the above functions; however, progressively, it may make the condition worse.

Aldosterone inhibitors

  • These medicines inhibit aldosterone activity selectively.
  • It acts independently of blocking angiotensin-renin.
  • Aldosterone re-infusion selectively can restore glomerular lesions and proteinuria.
  • There is a pathogenic action of aldosterone in progressing the renal illness.
  • Aldosterone through TGF synthesis regulation displays fibro genic characteristics, which is why blockage of aldosterone is considered. It has a negative impact on the glomerulus.

Medicines that are commonly used in this category

1-2 mg/kg- Spironolactone

This medicine is used as it is or in combination with any Ace inhibitor to get an enhanced reno-shielding effect.

Antithrombotics

  • These medicines aid in glomerular lesion development with their coagulation system. Fibrin deposition and intraglomerular coagulation are notable with this medicine.
  • Platelets mediate and amplify glomerular injury and enhance vascular permeability. It, in turn, facilitates the localization of glomerulus and in complex immune circulation.
  • Rivaroxaban is the current medicine used in this category for humans. It treats as well as prevents thrombosis. It focusses on the clot-bound factor and free Factor of thrombosis. It works by inhibiting both factors, thrombi development, and thrombin formation.

Other classes of drugs used in the condition of PLN

Antihypertensives
Vascular fibrosis, sodium retention, RAA system activation, renal vasodilators are restricted with the use of these categories of medicines.

Calcium channel blockers
These are combined and used with ACE inhibitors. These medicines dilate arterioles and the ACE inhibitor effect, eventually balancing them. This balances the gradient of pressure on the glomerulus. Currently, 0.1- 0.5 mg/kg Amlodipine is taken one time daily in this medicinal category.

Immunosuppressant
Using these medicines is for kidney histopathology. Azathioprine, Cyclophosphamide, Cyclosporine, along with corticosteroids, come into this category of medicines.

Omega 3 Fatty acids
These medicines protect renal activity. It gradually slows down the advancement of renal failure. This is done by restricting the generation of eicosanoids and cytokines. Their actions are limited to these medicines. About 150mg/kg in a day is recommended for renal patients.

Prognosis

Protein Losing Nephropathy has a median survival time-period of a month. When there are severe to moderate cases of renal failure, the survival period is still one month. If the root cause of Protein Losing Nephropathy condition is treated, then there is a resolution is possible with PLN. However, this is generally uncommon. With ACE inhibition use, the PLN impacted patients have extended their time of renal failure, and survival is extended too. This time of survival can be anywhere from 1-2 years, which is considered reasonably good.

Protein Takeway:
protein losing nephropathy

PLN or Protein Losing Nephropathy is a condition where glomeruli or kidney filters fail to shield the protein from passing through to the urine. This impacts the kidney, and there is a protein loss in the body. Restriction on protein is essential as this shall minimize the proteinuria amount. This way, the accumulation of protein within the renal tubules is inhibited. A renal diet with high-quality protein in appropriate quantities is suggested. A low sodium diet, medium to a low protein diet and non-processed foods are suggested to maintain kidney functioning appropriately.

Amongst all the treatments for PLN, ACE, or angiotensin-converting enzyme inhibition treatment is considered and proven effective. Since they minimize the renal flow of blood, they aid in minimizing PLN as well. Other drug considerations are ARBs, Omega-3 fatty acids, Immuno-suppressants, and others, as mentioned above.

The condition of PLN has several risk factors and complications associated with it. Its treatment is based on the cause of the condition. Your doctor will be able to assess the cause through proper medical diagnosis and be able to provide you the right treatment. The treatment would be to focus on the reduction of protein in the urine and to avoid or extend the renal failure time. The treatment is done based on the patient’s overall medical history and present condition. The condition of PLN can be prevented and treated by approaching the doctor at the right time and taking adequate treatment with consistent monitoring.

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