Bacterial Endocarditis and Associated Kidney Disease

There is very strong association between bacterial endocarditis or heart valve infection and kidney disease. Prior to the discovery, development and active use of antibiotics, the majority of the patients developed renal disease (kidney disease) as a consequence of subacute valvular infection. The incidence of clinical renal involvement has dropped significantly with the introduction of effective treatment of bacterial endocarditis with antibiotics. The assessment of renal involvement in bacterial endocarditis is quite difficult as transient changes in urine sediment are generally observed. There may be focal and segmental lesions with normal creatinine clearance. Intravenous drug users are at greater risk of developing bacterial endocarditis.

Staphylococcus aureus infection as the cause of bacterial endocarditis has been reported in majority of the cases that lead to a higher frequency of diffuse glomerular disease. The renal lesions associated with endocarditis involved embolization and infection. The renal lesions could also have immunological basis as immune complex deposits within glomeruli have been detected in majority of the cases. The involvement of complement (an immune response modulator protein in our blood) system during active disease (bacterial endocarditis) in association with immune complexes complicates the severity of intra-glomerular lesions. The two major categories of renal lesions found in patients affected by bacterial endocarditis are: (1) Focal segmental abnormality due to subacute infection and (2) Diffuse glomerular lesions in the patients with acute bacterial endocarditis mimicking the pattern of post-streptococcal glomerulonephritis. The electron micrograph (Fig-1) from the kidney biopsy of a patient with acute glomerulonephritis and acute bacterial endocarditis illustrates the subepithelial immune complex deposits.

Fig-1: Electron micrograph illustrating the hump shaped subepithelial immune complex deposits (D) alongside the glomerular basement membrane (GBM) and urinary space (US), during acute glomerulonephritis. Uranyl acetate and Lead citrate stain.

The assessment of renal involvement in endocarditis may be difficult diagnostic entity as only minor and transient changes are observed in urinary deposit with variable changes in blood biochemistry. The clinician must recognize the status of impaired cardiac output in the first stage and later workout the potential risk of treatment associated antibiotic nephrotoxicity. The assessment of renal function at the time of presentation of case could be helpful to rule out endocarditis associate renal disease or treatment associated antibiotic nephrotoxicity.

What Could Be The Cause Of Swelling On Face

The swelling on face or facial edema should be taken seriously if there is no history of insect bite, wasp sting or honey bee sting and when it is after a throat infection. The swelling on face or facial edema could be due to renal disorder (kidney disease). If on routine examination of urine of the patient, excretion of albumin or protein is detected; there is a need to consult a nephrologist for proper investigations. Blood biochemistry for blood urea, serum creatinine, serum proteins, serum electrophoresis, urine electrophoresis and 24-hour urinary protein should be done. Excretion of protein in 24-hours through urine will help the physician to assess the loss of proteins and possible course of action. Urine electrophoresis would show the type of protein being excreted in the urine. In a patient with nephrotic syndrome, serum electrophoresis would show hypoalbuminemia (low level of albumin in blood), hypogammaglobulinemia (low level of globulins in blood) and raised alpha-2 (a-2) globulin, and urine electrophoresis may show albuminuria (excretion of albumin in urine) or non-selective proteinuria (excretion of almost all the fractions of serum proteins in urine). Total serum protein and its fractions like albumin and globulin would show the altered albumin-globulin ratio. The normal albumin-globulin ratio (^Albumin/_Globulin) is 3:1 and it may be reversed in patients with swelling on face due to kidney disease.

The swelling on face or facial edema is directly associated with albuminuria (excretion of albumin in urine) and salt retention. The loss of blood albumin through urine hinders the return of fluid from the tissues into the blood and may thus lead to development of edema. It is well known that 68 to 70% weight of our body is due to water content in the blood and tissues. Around 12 to 14% of the total water volume of our body is in the blood and the rest is present in the tissues of the body. There is direct correlation between albuminuria (excretion of albumin in urine) and edema. Retention of Chloride is also a common accompaniment of edema. However, there may not be any retention of Chloride in majority of the cases with edema. The edema is perhaps the greatest problem confronting the students of nephrology. Pathological lesions in the kidney need to be evaluated microscopically through renal biopsy examination. Blood urea and serum creatinine may be normal. There may be salt retention without edema and edema without salt retention. The Chloride may collect in watery subcutaneous tissue due to some external factors also without involvement of any renal lesion.

Two forms of swelling on face or facial edema could be recognized and these are called nephritic edema and nephrotic edema. In nephritic edema the protein content of the edema fluid is over 1 gram/dl whereas in nephrotic edema the protein content of the edema fluid is always less than 0.1 gram/dl. Nephritic edema occurs in acute glomerulonephritis. The capillaries in the subcutaneous tissue become more permeable leading to leakage of proteins in the extra cellular fluid. Nephrotic edema occurs in the wet nephritis or second stage of nephritis, in nephrosis and also in renal amyloidosis. The edema is caused due to the great fall in the osmotic pressure of the blood due to constant loss of protein in urine; so, the fluid from the blood vessels escapes into the tissues in an effort to correct the viscosity of blood plasma.

How Electrolyte Imbalance Causes Renal Disease Or Renal Disease Leads To Electrolyte Imbalance

Electrolytes or essential ions should always be in the state of homoeostasis. The Normal or standard range of electrolytes reflects the normal functional status of our kidneys. Our kidneys play a vital role in preserving the internal environment while excreting the waste products of metabolism, extra water and electrolytes. There is two way selectivity between the cause and effect between the electrolytes (essential ions) and renal disorder (kidney disease). Depletion of Sodium (Na⁺) or Potassium (K⁺) or Calcium (Ca⁺⁺) through excessive urinary excretion may cause renal failure or renal failure may lead to depletion of these ions or electrolytes in the blood plasma.

The renal tubules play a vital role in regulation and preservation of water and electrolytes. The function of tubular epithelium and tubular enzymes is under the control of hormones of some endocrine glands. Suboptimal response of tubular enzymes or over production of corresponding hormone may cause renal disorder (kidney disease). Anti-diuretic hormone of pituitary gland, aldosterone and parathyroid hormone affect the renal tubules to regulate and preserve the water and electrolytes. Potassium (K⁺) content of the cells plays a critical role in retention or excretion of potassium. The glomeruli of our kidneys excrete Potassium (K⁺) in glomerular filtrate and tubular epithelial cells also excrete Potassium (K⁺) by ion exchange in which Potassium (K⁺) of tubular cells is exchanged by Sodium (Na⁺) of glomerular filtrate. Re-absorption is controlled by proximal tubules whereas the excretion is controlled by distal tubules.

Low dietary intake, fever, trauma, or hemolysis leads to tissue catabolism in patients with anuria (no urine output) leading to release of more Potassium (K⁺) from the cells. In these patients Potassium (K⁺) concentration in blood may reach lethal level (more than 100 mEq/litre). Normal level of Potassium (K⁺) in serum is 5.5 mEq/litre. The clinical features of hyperkalemia (high level of Potassium in blood) could be mainly cardiac (bradycardia or arrhythmia) with significant changes in electrocardiogram (ECG). Potassium (K⁺) depletion may be renal or non-renal in origin and may be suspected when pronounced muscular weakness and lethargy is associated with electrolyte imbalance. Commonest cause of Potassium (K⁺) deficiency could be the uncontrolled use of diuretics for the treatment of congestive heart failure. Potassium (K⁺) deficiency leads to vacuolation of tubular epithelium in proximal tubules (known as clear cell nephropathy). The associated renal changes are reversible with correction in Potassium (K⁺) level in blood/serum. Aldosterone is Sodium (Na⁺) retaining adrenal corticoid secreted by adrenal cortex. Excessive secretion of this corticoid as in cases of adenoma of adrenal cortex may lead to increase in the level of Sodium (Na⁺) and extracellular fluid volume and altered function of Sodium pump. In usual Potassium (K⁺) losing nephropathies there is failure of hydrogen ion excretion in association with the failure of retention or conservation of Potassium (K⁺).

Hypercalcemia (high level of Calcium in blood) as seen in primary hyperparathyroidism, sarcoidosis, excessive vitamin D intake or idiopathic hypercalcemia of infants, may also result in renal damage. Hypercalcemia is also a feature of acute osteoporosis of multiple myeloma and matastatic carcinomatosis of bone. Hypercalcemia could be a lethal complication associated with sarcoidosis but may successfully be reversed with timely steroid therapy. The serum level of Calcium (Ca⁺⁺) may return to normal in a few weeks but the reversal of renal insufficiency may take a year or longer. Calcium (Ca⁺⁺) is retained in our body in the form of Calcium phosphate. The hormone like action of vitamin D during excessive intake, causes increased excretion of phosphorus in urine, unsaturation of serum Calcium phosphate, demineralization of bone leading to increased level of Calcium in blood and increased loss of Calcium in urine. Hypercalcemia could cause nephrocalcinosis leading to renal insufficiency.

Renal Biopsy Procedure: Complications

Pathological lesions in affected kidneys of patients with renal disorder (kidney disease) could only be evaluated through histological, immunofluorescence and ultrastructural examination of renal biopsy. The renal biopsy (kidney biopsy) procedure as percutaneous needle biopsy was established long back in 1949 and has undergone a great refinement. At present, a large number of medical centers have been performing ultrasound guided percutaneous renal biopsy procedure for the diagnostic and prognostic evaluation of renal tissue. However, majority of the centers lack the facility of electron microscopy for ultrastructural examination of renal biopsies. Cases with microscopic hematuria (blood in urine) and hereditary nephropathies need ultrastructural examination of renal biopsy (kidney biopsy) for an accurate diagnosis. In expert hands the procedure is as safe as incision biopsy or percutaneous biopsy of liver, but post biopsy complications in rare cases could not be avoided. Hematuria (blood in urine) is a common complication and could rarely necessitate blood transfusion. There are 0.01 percent (1 in 10,000) chances of severe hemorrhage secondary to puncture leading to compulsive nephrectomy (surgical removal of kidney). Uncommon complications could be sepsis and hypertension due to perirenal hematoma. Renal biopsy (kidney biopsy) procedure is not advisable for patients with only one functional kidney.

Oliguria Or Anuria: Cause May Be Renal Or Non-Renal

The term oliguria means low urine output and anuria stands for no urine output. The oliguria or anuria could be due to renal disease (kidney disease) or non-renal (non kidney) problem. The four possible causes which probably lead to oliguria or anuria are listed below:

1. Obstruction in a kidney: Obstruction in a kidney or lower urinary track may cause oliguria or anuria. Debris of epithelial cell may block the renal tubules. Hemoglobin or myoglobin pigments or crystals of some drugs have also been documented as the possible cause of casts blocking the renal tubules. Interstitial edema (swelling of interstitial tissue in kidney) could also compress tubules thereby leading to impairment of tubular function. Net result of any sort of obstruction in a kidney is the oliguria which could lead to a grave situation i.e. anuria.
2. Dehydration: Continued vomiting, severe diarrhea or profuse sweating may lead to dehydration resulting in oliguria or complete cessation of urine i.e. anuria.
3. Peripheral circulatory collapse: Peripheral circulatory collapse may occur due to post-operative surgical shock leading to reduced renal blood flow and glomerular filtration rate (GFR) resulting in anuria as the tubules reabsorb whatsoever the glomerular filtrate is produced by glomeruli.
4. Degeneration of tubular epithelium: Degeneration of tubular epithelium causes detachment of epithelium from tubular basement membrane (TBM) resulting in massive loss of tubular epithelial cells. The loss of tubular epithelium leads to loss of physiological barrier between glomerular filtrate in tubules and very strong osmotic pull of plasma in the peri-tubular capillaries (PTC), hence any glomerular filtrate present in tubules is sucked out by PTC, leading to anuria. Mercuric chloride poisoning may cause this type of anuria, however, it could be reversible and epithelial lining of tubules be restored within about two weeks. Avoid tasting unknown and unspecified chemicals to save your kidneys and life.

Control Diabetes To Save Your Vision And Kidneys

The global diabetic community is always at risk of diabetes associated complications. The disease may be hereditary or lifestyle associated. The growing number of cases per year among children and adolescents is a cause of concern. World Diabetes Day is celebrated on November every year in the memory of Sir Frederick Banting who discovered insulin, with an aim of awareness among masses about the alarming rise of diabetes through out the world. Knowledge about the 'warning signs of diabetes' and its control could definitely help us to control diabetes and diabetes associated complications. Abnormal carbohydrate metabolism leads to diabetes. The carbohydrates in the form of starch and sugars are acted upon by the enzymes of the saliva in our mouth and pancreatic and intestinal juices in the small intestine. The action of various digestive enzymes converts the complex sugars into simple sugar such as glucose. The glucose is absorbed by villi of the small intestine, passes into the blood capillaries, and is carried by the portal vein to the liver, where excess sugar is converted into glycogen and stored in the liver cells until required for use. The amount of starch and complex sugars and other chemicals we eat, influence our metabolism. Insulin is called anti-diabetic hormone and plays an important role in the carbohydrate metabolism. Insulin is secreted by pancreas and governs the ability of the cells of the body to absorb and use glucose and fats. Diabetes may be non-insulin dependent or insulin dependant depending on the involvement of insulin. Preservatives in food stuffs, coloring agents and taste maker chemicals could be the main cause of diabetes in children and adolescents.

Diabetes associated complications are related to duration of diabetes. The longer is the duration of diabetes, the greater is the risk of diabetic complications. It has been documented that 80 per cent of the patients who suffer from diabetes for more than 15 years would have damage to retina. The diabetic retinopathy is a serious diabetic complication. Diabetic retinopathy damages the blood vessels of the retina and could lead to blindness. Early detection of diabetes and its control through regular exercise, medication and change in lifestyle and food habits is the key to avoiding diabetic complications. To reduce the incidence of various diabetic complications, it is important to keep the blood sugar levels under control and have regular checkup. Diabetic retinopathy may be non-proliferative diabetic retinopathy (NPDR) or if unchecked that may lead to proliferative diabetic retinopathy (PDR). Lack of blood supply to retina in proliferative diabetic retinopathy may lead to complete vision loss.

Diabetic nephropathy, a kidney disease is another serious complication associated with diabetes. Kidneys play a vital role in our body to excrete toxic waste products of metabolism and to maintain balance of electrolytes and water as well. Uncontrolled diabetes causes irreversible damage to renal glomeruli, the filtration units of our kidneys. There is a great need for the diabetic friends to control diabetes through conventional and non conventional methods to lead a healthy and cheerful life without much complication. All diabetic patients must have a medical and eye examination at regular intervals to avoid diabetes associated complications.

Albumin & Casts in Urine and Associated Renal Lesions

Urine analysis is the cheapest and routine investigation which could be of great help to the clinician to reach at a diagnosis of a complex renal disorder. Albuminuria (excretion of albumin in urine) detected on heat test of the urine and the casts detected on microscopic examination of first morning specimen of urine reveal a lot about the associated renal lesions (pathological changes in kidney). Albuminuria we know definitely to be glomerular origin, although the tubules may also play their part in its production. It seems probable that this is mainly due to the glomerular basement membrane (GBM) which separates the epithelium of the tuft from the endothelium lining the capillaries, with increase of its permeability.

Casts are the microscopic accumulations of cells or coagulated proteins or lipids. Casts if present could be detected on microscopic examination of deposit obtained after centrifugation of urine. The casts must also be traced to the glomerulus, at least the essential hyaline matrix of the cast composed of coagulated albumin. Again the tubules add their contribution in the shape of epithelial cells and fatty and granular detritus which give to the casts their characteristic appearance. Careful examination casts is as informative as blood biochemistry investigations in cases of kidney disease. The cast gives a picture of the degenerative changes in the tubules. A hyaline cast indicates slight glomerular leakage without active tubular degeneration. Cellular casts denote marked activity of the morbid process. Granular casts denote moderate activity. The admixture of red blood cells (RBCs) is a sign of glomerular hemorrhage. We find that the study of casts is of remarkable importance in assessing the prognosis of a renal disorder. As long as there is considerable activity there is a scope for improvement. For such a study to be of value, the urine should be fresh. If the urine is alkaline or has been allowed to stand for long time, the casts may largely disappear. The absence of casts in an alkaline urine has not the same significance as when the urine is acidic. The acidity of the urine assists in the formation of casts. Deposition of casts in the tubules may lead to oliguria (low output of urine) leading to edema.

Kidney Biopsy and Its Diagnostic Relevance

The entire focus of the modern medicine is to find a rational treatment for various ailments. The accurate diagnosis is the key to specific therapy for a disease. Kidney biopsy evaluation is of paramount importance to assess the pathological lesions associated with the disordered renal function and for deciding the course of a particular treatment regimen. Percutaneous needle biopsy of kidney was introduced by Iversen in 1949. Kidney biopsy, need not to be performed in every case with symptoms of renal disease. For kidney biopsy procedure, the patients must be selected carefully, excluding cases with only one functional kidney. Patient is briefly hospitalized for taking kidney biopsy. The blood coagulation parameters of the patient must be within normal limits. Needle biopsy of kidney is performed by the Nephrologist under ultrasound guidance, preserved in the suitable fixatives and immediately rushed to the Pathology Laboratory for histological, immunofluorescence and ultrastructural examination. Composite study of the kidney biopsy by the three methods mentioned above is essential to establish an accurate diagnosis of renal disorder or kidney disease and evolution of a particular renal disorder. A renal biopsy (kidney biopsy) must contain glomeruli to be considered adequate for achieving a diagnosis. Generally, the specimen is considered adequate when atleast 5 glomeruli with corresponding tubules are present. Many pathologists believe that interpretation of renal biopsies is extremely difficult. Obviously it has become more complex over the years because of changing approaches to the classification of glomerular diseases. A thorough knowledge of normal histology and ultrastructure of renal components is essential to recognize any alteration in various components of the kidney. An accurate diagnosis could only be achieved through clinicopathological correlation and consideration of family history of patient in cases of congenital and hereditary glomerular diseases.

Adverse Drug Reaction and Kidney

Adverse Drug Reaction (ADR) is defined as any unintended and undesired effect of a duly prescribed drug which occurs at a dose used in humans for prophylactic, therapeutic or diagnostic purposes. All drugs taken externally or internally produce some undesirable effects along with their beneficial effects. Adverse events that occur as a result of drug use may range from local reaction, respiratory distress, renal lesions/damage or liver function impairment to serious life threatening condition. The liver and kidney are the organs which bear the brunt of majority of adverse drug reactions (ADRs) as these are associated with the drug metabolism and clearing from the body. The nature of the beneficial effects of a drug is predictable, but the nature of adverse reaction could be predictable to some extent otherwise unpredictable. The term drug here means any substance or product used to modify or explore physiological system and pathological states for the benefit of the patient/recipient. The health products considered to be drugs include vaccines, food supplements, blood and blood products, herbals, traditional or complementary medicines, pace maker devices and implants. Mismatched blood would cause transfusion reaction with life threatening implications. Blood products like platelet rich plasma (PRP) which is normally infused in patients suffering from Dengue virus infection may lead to the development of antibodies against human leukocyte antigens (HLAs) as platelets carry Major Histocompatibilty Complex, class-I (MHC class-I) antigens i.e. HLA-A, HLA-B, & HLA-C antigens at their surface and these antibodies may lead to lyses of platelets and thrombocytopenia (decreased platelet count) at a later stage.

Regulatory approval to market drug is usually based on the results of controlled clinical trials, as such, these short term studies in a specific population may not be sufficient to explore the ill effects of a particular drug. The ADR monitoring begins with the earliest administration of a drug to man and continues throughout, as long as a drug is on prescription list of clinicians.

Long term surveillance studies are also being undertaken to evaluate effectiveness and safety of a drug in various subpopulations such as, children, elderly patients and patients with associated ailments like impaired liver function, kidney disease and diabetes. In order to highlight the ADR events, the pharmacovigilance is important. The ADR events include the events due to non-compliance, drug interactions with co-administered drugs and drug over dosages and adverse effect of the drug per se. As per the data available to-date, about 6% of Emergency visits are related to ADRs and about 0.1% of these could be life threatening.

Can We Prevent Adverse Drug Reactions: Yes, a lot of these ADRs are preventable, most probably those resulting from mere ignorance of route of administration or non-compliance. There are ADR cases wherein patients have swallowed the tablets prescribed for intra vaginal infection.

How and Whom to Report ADR: Independent reporting can be undertaken by any one who is prescribing a drug, administering a drug or consuming a duly prescribed drug. This type of reporting is called Voluntary Reporting or Spontaneous Reporting. One should be ready with the following information while reporting ADR: Patient"s short name, age, sex, height, weight, trade name of drug, manufacturer, date of manufacture, date of expiry, mode of administration, type of reaction, duration of administration, route of use, date of reaction, date of recovery and associated medication etc. Adverse Drug Reaction should be reported to the Pharmacovigilance Center. There are National, Zonal, Regional and Peripheral Pharmacovigilance Centers in all the countries. The matter can also be reported to the Drug Controller General of the Country or reported directly to the United States FDA. For reporting the ADR or adverse events to International Regulatory Authority like US FDA one can use online reporting facility at the  website http://www.fda.gov/medwatch/ .  Go to the FDA-Medwatch website and visit the link-Medical Product Reporting for reporting adverse drug reaction or adverse events.